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To document polyp formation in the sinus mucosa, the authors of this study subjected New Zealand white rabbits to different modes of manipulation intended to induce inflammation of the maxillary sinus. These manipulations included a combination of bacterial infection and mechanical trauma, the deposition of agarose into the sinus cavity, and the deposition of N-formyl-methionyl-leucyl-phenylalanine, a chemotactic peptide, into the sinus cavity. A majority of animals developed polyps, which were examined by light and electron microscopy. Polyp formation appears to involve epithelial disruption and the migration of immature branching epithelium. While part of the migrating epithelium eventually covers the mucosal defect, other branches spread into the underlying connective tissue, where intraepithelial microcavities with a differentiated, ciliated lining are formed. Fusing cavities separate the developing polyp body from the adjacent mucosa. With the described method, mucosal polyps can be induced with high reproducibility. [ABSTRACT FROM AUTHOR]

Objective: The study evaluated the possible differences in the repair of cricoid cartilage defects treated with recombinant human BMP-2 in young and adult rabbits., Methods: A cricoid defect rabbit model was used. Thirty rabbits were randomly divided into eight groups. Two groups of young rabbits and two groups of adult rabbits were treated with rhBMP-2 delivered on an absorbable collagen sponge, while the other two groups of young rabbits and two groups of adult rabbits were used as controls. The rabbits were killed at 1 week or 4 weeks after surgery. A histomorphometric analysis and an evaluation of the expression of collagen types I, II, and X, and proliferating cell nuclear antigen as well as a study of distribution of calcified matrix, were performed., Results: rhBMP-2 induced a marked chondrogenesis in both experimental age groups. However, in young rabbits the newly formed cartilage appeared more elongate, and the length of perichondrium involved was greater. The host cricoid cartilage of adult rabbits was calcified in large areas and displayed a strong matrix expression of collagen type X as well as collagen type I in the perichondrium, compared to the cricoid of young rabbits. In spite of these differences no immunohistochemical differences were found in the newly formed cartilage of both age groups treated with rhBMP-2. The cricoid cartilage defect was filled with new bone at 4 weeks in both age groups treated with rhBMP-2. New bone tissue had a well-defined trabecular structure., Conclusions: rhBMP-2 triggers appositional cartilage growth from the cricoid perichondrium of young rabbits more easily than from that of adult rabbits. The new bone induced by rhBMP-2 showed a similar immunohistochemical and morphological pattern in both age groups of rabbits.

We determined the origin of new cartilage and new bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) at the site of cricoid cartilage defects in rabbits randomly divided into eight groups. The cricoid cartilage was split vertically along the anterior midline and a strip was excised from the anterior part of the cricoid cartilage in all rabbits. The perichondrium from the anterior part of the cricoid cartilage was trimmed off in four groups; two groups treated with rhBMP-2 and two control groups. In four other groups, the anterior perichondrium was detached and used as a flap with two groups treated with rhBMP-2 and two groups serving as controls. The rabbits were killed 1 week or 4 weeks after surgery. The larynges were removed, fixed and sectioned, and the sections were stained for light microscopy using various cytochemical and immunological techniques. New cartilage was only present close to the host perichondrium adherent to cricoid cartilage in rabbits treated with rhBMP-2. New bone was present 4 weeks after surgery, although calcified matrix and alkaline phosphatase activity could be detected at the site of cricoid defects as early as 1 week after surgery. The cell proliferation marker Ki-67 was strongly expressed in granulation tissue and bone marrow, and it was moderately expressed in muscles adjacent to the cricoid cartilage in rhBMP-2-treated specimens. BMP receptors were strongly expressed in cartilage and moderately expressed in adjacent muscles. We conclude that new cartilage originates from the mesenchymal progenitor cells of host perichondrium adherent to cricoid cartilage in rabbits treated with rhBMP-2. New bone may originate from local muscle.

Objective: Bone morphogenetic protein-2 offers potential benefits for cartilage regeneration. We investigated the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the regeneration of laryngeal cartilage and respiratory epithelium in a rabbit model., Material and Methods: We used a cricoid defect rabbit model. Twenty-four rabbits were randomly divided into four equal groups. Two groups were treated with 5 microg of rhBMP-2 delivered on an absorbable collagen sponge and the other two groups were used as controls. One group of treated rabbits and one group of control rabbits were euthanized 1 week after surgery, while the others were euthanized 4 weeks after surgery. The healing pattern of the laryngeal wound was evaluated by means of histomorphometry., Results: Regeneration of both the epithelial layer and cartilage was significantly better in rabbits treated with rhBMP-2. Four weeks after surgery, the cricoid cartilage defect was completely repaired by new cartilage and new bone in rabbits treated with rhBMP-2. Furthermore, the lining respiratory epithelium healed more rapidly in treated rabbits., Conclusion: rhBMP-2, delivered via an absorbable collagen sponge, induces complete regeneration and repair of rabbit cricoid cartilage defects. It also induces faster relining and regeneration of airway epithelium than in control rabbits.

We examined the structural characteristics of repair tissue induced by recombinant human bone morphogenetic protein-2 in a rabbit model of laryngotracheal reconstruction. Twenty-four New Zealand White rabbits were randomly divided into four groups of six rabbits. Two groups were treated with recombinant human bone morphogenetic protein-2 delivered on an absorbable collagen sponge, while two groups were used as controls. Rabbits were euthanized at 1 and 4 weeks after surgery. The larynx was removed, fixed, and sectioned. The sections were stained with hematoxylin-eosin, safranine O/fast green, and immunostained with an antibody for tissue inhibitor of metalloproteinases-1. In rabbits treated with bone morphogenetic protein-2, the defects were filled with new cartilage and bone at 4 weeks after surgery. There were no discontinuities or gaps at the margins of the cartilage defects. Proteoglycans were synthesized in new cartilage in rabbits treated with bone morphogenetic protein-2, and were present 4 weeks after surgery. The general aspects of the vascular pattern and the pattern of tissue inhibitor of metalloproteinases-1 expression were similar in control and treated rabbits, both 1 week and 4 weeks after surgery. The repair tissue induced by recombinant human bone morphogenetic protein-2 consisted of new cartilage and bone perfectly integrated with host tissue at the site of the cricoid cartilage defects. This new cartilage was able to mature and produce proteoglycans.

In the rat larynx, plasma exudation and edema formation were studied by light and electron microscopy after i.v. injections of the mast cell activator compound 48/80, substance P, and capsaicin. The morphological effects of substance P and capsaicin on connective tissue mast cells in vivo were also examined. Of the drugs tested, only compound 48/80 degranulated the connective tissue mast cells. All drugs induced a subepithelial plasma exudation in the subglottic region, with edema in the lamina propria and widened intraepithelial intercellular spaces, though the tight junction regions seemed intact. In the epiglottis, 10 min after compound 48/80 injection, there was edema in the lamina propria on the lingual side, with an intact and tight epithelial lining. No morphological sign of edema was found in the epiglottis after injection of substance P or capsaicin. The pronounced effect found in the epiglottic region after compound 48/80 injection was due to the release of mediators such as histamine and 5-hydroxytryptamine from the connective tissue mast cells. This study supports the belief that substance P in vivo mediates an increased vascular permeability by a direct effect on the blood vessels - a mechanism distinct from mast cell degranulation.

Lectin expression in both normal and inflamed sinus mucosa in rabbit was investigated histochemically. A different staining pattern was observed in the inflamed mucosa, i.e. the degree of staining reactivity with Canavalia ensiformis (ConA) decreased, whereas staining with Ulex europaeus agglutinin-I (UEA-I), Arachis hypoga (PNA) with neuraminidase pretreatment and Triticum vulgaris (WGA) intensified, indicating an enhanced fucosylation as well as sialylation. Goblet cells were stained with UEA-I, WGA, PNA and PNA with neuraminidase pretreatment, but scarcely with ConA. Positive PNA staining of basal cells and epithelial secretory granules was observed in the inflamed mucosa, especially close to areas where goblet cell development was prolific. It was therefore assumed that basal cells can differentiate into goblet cells-through epithelial secretory cells accompanied by sialylation and/or sulphonation of their mucins. It is concluded that the changes in glycoconjugate expression as well as goblet cell development in the inflamed mucosa are of importance for both local host resistance and defence mechanisms against microorganisms during the early stages of the inflammatory process.

To evaluate the pattern of goblet cell differentiation in sinus mucosa in response to external stimuli, New Zealand White rabbits were subjected to either experimental sinusitis or topical capsalcin application. Sinus mucosa was examined by light microscopy after serial sectioning, whole-mount preparation or immunohistochemistry. The mucosa was also examined by electron microscopy after perfusion fixation or high-pressure freezing. While goblet cells were normally very scarce in the healthy rabbit maxillary sinus mucosa, such cells were frequent after experimental sinusitis or topical capsaicin application. The process of goblet cell differentiation seems to follow a sequential path where serous secretory cells start to produce an increasing amount of mucous granules which appear electron lucent after conventional fixation. Parallel to this shift in secretion production, the cell assumes a bulging appearance after conventional fixation. It is concluded that newly formed goblet cells are recruited from intermediate secretory cell stages rather than from ciliated cells.

The effect of airway infection on neurogenic inflammation is not known. The present study examines the effect of Mycoplasma pulmonis infection on the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) in the trigeminal ganglion and in the mucosa of the nose and trachea in rats. We compared germ-free (GF), conventionally raised (CV) and specific pathogen-free (SPF) rats. The concentrations of SP and CGRP in the nasal mucosa were assessed with immunohistochemistry, and their prohormonal transcripts in the trigeminal ganglion were assessed with Northern blot. Mucosa was also processed for light microscopy and electron microscopy. SP-like immunoreactivity was greater in the nasal mucosa of infected animals than in uninfected controls. CGRP-like immunoreactivity was greater in the nasal septum, but not in the nasal turbinate, of infected than uninfected animals. In contrast, no change was evident in the expression levels of the prohormonal transcripts in the trigeminal ganglion. Infected nasal and tracheal mucosa was oedematous and locally infiltrated with inflammatory cells. In the nose of uninfected GF rats, subepithelial lymphoid aggregations were scarce and appeared inactive. We conclude that Mycoplasma pulmonis infection results in increased immunoreactivity of substance P, probably within nerves. There was no clear evidence of increased synthesis of the precursors of substance P and calcitonin gene-related peptide.

More than 200 years have passed since the pulsion diverticulum of hypopharynx was first described. This paper reviews different opinions on its etiology over the centuries. The German pathologist F.A. von Zenker, who successfully pursued research on a variety of topics, is often associated with this diverticulum through his classical work from 1867 "Krankheiten des Oesophagus", which deals with the pathogenesis and clinical presentations of this herniation of the posterior mucosal wall. Numerous surgical techniques, which have been practised mainly during this century, are also reviewed. Different options of endoscopic surgery, which is presently the preferred approach at many medical centers, are described and discussed. Our own experience of endoscopic surgery in patients with Zenker's diverticulum is also presented.

To study the possible autocrine growth stimulation of cholesteatoma epithelium, the expression of transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) in middle ear cholesteatoma was investigated by immunohistochemical staining techniques. Twenty cholesteatoma samples obtained at operation and six normal skin specimens collected from the external ear canal were used in the study. Immunostaining for TGF-alpha showed a diffuse cytoplasmic staining pattern. It was weakly expressed in the basal layer of the normal epidermal epithelium but was more strongly expressed in all cholesteatoma specimens. EGFR showed a dot-like/diffuse cytoplasmic and cell membrane staining pattern. EGFR-positive cells were seen in the basal layer of normal epidermis. In the cholesteatoma specimens, expression of EGFR was not only confined to the basal layer but persisted into the upper layers of the epithelium. Our findings indicate that an autocrine growth stimulation by TGF-alpha and EGFR may contribute to the unrestrained growth of cholesteatoma epithelium in the middle ear cavity.

The expression of epithelial markers (cytokeratins, Filaggrin, BerEp4 and EMA), collagen IV and Ki67 was studied immunohistochemically in cholesteatoma and compared with that in epidermis of meatal skin, squamous epithelium of eardrum and simple epithelium of middle ear mucosa. MNF116 (cytokeratin 10, 17, 18) stained the full layer of normal epithelium and all cholesteatoma specimens. CK10 and Filaggrin were expressed in the upper layer of epidermis but more diffusely in cholesteatoma. BerEp4 was found in the basal layer of normal epithelium but was detected in most epithelial cells in cholesteatoma matrix. Variability was observed in EMA and CK14 immunostaining. Collagen IV was localized in the basement membrane of normal epithelium with a continuously staining pattern, an observation also made in the cholesteatomas studied. However, in one of these small areas the basement membrane was not stained with collagen IV. Ki67 was expressed in nuclei of the cells in the basal layer of normal epithelium but extended to epithelial cells in the upper layers of cholesteatoma matrix. The results of the present study indicate that the expression pattern of epithelial markers in cholesteatoma corresponds to that in normal epidermis. The increasing expression of BerEp4 and Ki67 confirms the hyperproliferative nature of cholesteatoma. Whether or not the lack of expression of collagen IV in one of the cholesteatomas reflects a true degradation of the basement membrane needs further investigation in extended materials.

Unilateral maxillary sinusitis was experimentally induced in New Zealand White rabbits with Streptococcus pneumoniae serotype 3, Bacteroides fragilis NCTC 9343, and Staphylococcus aureus V8. In another group of rabbits, sinusitis was induced by blocking of the sinus ostium only. Bacteriologic and light microscopic analysis was performed after 5 days to 1 month. Granulation-like polyps developed after deep mucosal inflammatory trauma initiating fibroblast proliferation, angiogenesis, and epithelial migration to cover the polyp. In regions of a more superficial trauma-characterized by epithelial desquamation and fibroblast growth-proliferation and differentiation of basal cells resulted in the formation of microcavities dissecting off edematous polyps. Polyps could be found in all sinusitis groups, irrespective of inducing agent. The cellular events of polyp formation appear to be the result of a continuous inflammatory reaction and are not directly related to the presence of a certain microorganism. Instead, the potential of any microorganism to induce a deep mucosal trauma or epithelial desquamation seems essential for its ability to initiate polyp formation.

Rabbit maxillary sinuses were inoculated with Streptococcus pneumoniae and Bacteroides fragilis, and the histologic response in the sinus mucosa was observed over a 12-week period. An increased height of the cylindric cells and hyperplasia of the basal cells were frequent findings irrespective of the pathogen inoculated. The disease was found to influence the character of the secretory product from epithelial secretory cells and to degranulate the subepithelial glands. Ciliary loss was a transitional finding. A reduction in the number of mitochondria, the occurrence of deformed short microvilli, and cytoplasmic blebbing were seen in the cells devoid of normal cilia. It is inferred from this study that pneumococcal sinusitis in rabbits is a self-limiting process, and the mucosal sequelae of the acute infection are persisting goblet cells, slight focal fibrosis, and edema. Inoculation with B fragilis produces a chronic inflammatory process, with infiltration of mononuclear cells, luminal dilatation of the glands exhibiting zymogen granule depletion, and an increased thickness of the whole mucosal layer.

A rapid regeneration of the epithelium takes place in the maxillary sinus in rabbits after experimental operative removal of the mucosa. Two weeks postoperatively the previously denuded areas have reepithelialized. The subepithelial glands, however, do not seem to regenerate. The normal sinus mucosa contains numerous serous glands in the lamina propria, but in the regenerated mucosa these glands are replaced by dense connective tissue. Atypical glands and polyp formations are sometimes encountered, but goblet cells are sparse. Furthermore, the sinus cavity on the operated side is reduced in size compared with the nonoperated side because of fibrosis and periosteal reactions including bone degradation and neogenesis. This study indicates that although the mucosa is reepithelialized within 2 weeks, the regeneration of the lamina propria is incomplete, and reactive cellular processes such as bone remodeling, fibroblast proliferation, and formation of polyps and "atypical glands" are characteristic of regenerating mucosa.

Experimental anaerobic maxillary sinusitis was induced in New Zealand White rabbits by blocking the ostium and inoculating Bacteroides fragilis, strain NCTC 9343. The animals were examined histologically and bacteriologically after 5 days, and 2, 3 and 4 weeks. All the infected sinuses displayed signs of moderate or severe inflammation throughout the study period. Ciliary damage and desquamation, hyperplasia and metaplasia of the epithelium were characteristic features. Furthermore, heavy leukocyte- and, particularly, round cell-infiltration, fibrosis, periosteal hyperplasia and bone degradation and -formation were also frequently encountered. The secretory cell count in the epithelium increased, including the regeneration of goblet cells. After 4 weeks no obvious recovery could be seen, and the inducing microorganism was re-isolated in the majority of cases. In comparison with experimental pneumococcal sinusitis, the B. fragilis infection exerts a more prolonged and severe inflammation.

Unilateral maxillary sinusitis was induced in 30 New Zealand White rabbits with Streptococcus pneumoniae or Bacteroides fragilis. In another group of 15 rabbits without infection, the sinus mucosa was surgically removed in defined areas. In both series, the sinuses were serially sectioned for histological analysis of the cellular regenerative capacity. In maxillary sinusitis induced by Bacteroides fragilis, an inflammatory and also reparative process involving all mucosal layers including the underlying periosteum was seen. The more superficial trauma as found in pneumococcal sinusitis eventually led to restitution ad integrum. Following surgical removal, the denuded sinus-lining was reepithelized by a flattened ciliated epithelium on a lamina propria displaying fibrosis and lacking serous glands. The restoration of the rabbit maxillary sinus mucosa after surgical trauma thus leads to structural abnormalities of the epithelium as well as the lamina propria, and these changes are likely to interfere with the normal function of the sinus mucosa.

Concentrations of the two optic isomers of lactate (D- and L-form) as well as glucose, succinate, acetate, butyrate, isovalerate and valerate were examined in purulent sinus secretions. The samples were obtained from rabbit maxillary sinuses, experimentally infected with Streptococcus pneumoniae or Bacteroides fragilis. More soluble acids such as acetate displayed relatively low levels in the secretion, despite a high microbial production. A substantial increase in D-lactate concentration was found in secretions only the first day after induction of pneumococcal sinusitis, and not in bacteroides sinusitis. L-lactate levels were particularly high in secretions of a marked purulent character, and this isomer can be considered as indicator of anaerobic glycolysis in the leukocytes. Less diffusible fatty acids such as butyrate and isovalerate accumulated in the secretion, in spite of a relatively lower production rate, and are thus more reliable indicators of bacterial metabolism.

Experimental acute sinusitis can be induced in New Zealand white rabbits by Streptococcus pneumoniae serotype 3, or the anaerobe Bacteroides fragilis, after blocking of the sinus ostium. Histological examination of the sinus mucosa in both models reveals edema, dilated venules, leukocytic infiltration, goblet cell formation, as well as localized epithelial lesions. In comparison the bacteroides sinusitis enhances a more pronounced and long-lasting tissue reaction, including periosteal thickening and new bone formation. The sinus mucosal blood flow as measured with microspheres Sn113 is increased as compared to control side in pneumococcal sinusitis. An increased lactate concentration of sinus secretions as well as in the pathological sinus mucosa indicates an anaerobic metabolism. Furthermore, a decreased ATP-content of the sinus mucosa suggests an energy depletion which could impair epithelial function. The anaerobic milieu of the sinus secretion is probably created by the leukocytes as analyzed by the separation of the D- and L-form of lactate.

The distribution of mast cells in the rat larynx was studied at a light microscopic level in relation to nerve fibers showing substance P (SP)- and calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) and ultrastructurally in relation to unmyelinated nerve fibers. Connective tissue mast cells (CTMC), demonstrated by staining for avidin-peroxidase and immunohistochemical staining for 5-hydroxytryptamine (5-HT), were localized in the lamina propria. Alcian blue and toluidine blue revealed mast cells in the epithelium and the lamina propria. The mast cells showed similar regional differences in their distribution as fibers showing SP- and CGRP-LI. A large or moderate number of cells was found on the laryngeal side of the epiglottis, in the ventral recess and in the aryepiglottic folds. No mast cells were found in the vocal cords. In addition, a large number of cells showing 5-HT-LI were observed in the subglottic epithelium but not in the supraglottic and the glottic epithelia. Ultrastructurally and by use of SP- and CGRP-immunohistochemistry, nerve fibers were sometimes observed close to the mast cells. These findings may be of importance in the understanding of laryngeal pathophysiological events.

Biopsy samples from the maxillary sinus mucosa of patients with purulent, non-purulent and recurrent sinusitis were studied histologically and compared with those from a maxillary sinus of patients with no previous history of sinus disease on the side of sampling. Basement membrane thickening, atypical gland formation, goblet cell hyperplasia, mononuclear inflammatory cell infiltration and subepithelial oedema were observed in all groups irrespective of the appearance of the effusion. Although the inflammatory variables in selected areas of the mucosa seemed to show an increase in severity with the increasingly severe forms of sinusitis, neither the endoscopic mucosal appearance nor the nature of the sinus effusion corresponded to any specific histological pattern.

A quantitative electron microscopic study was performed in a case of parotid oncocytoma. The mean nuclear radius was estimated to be 3.4 mu, and the mean nuclear volume 171 cu mu. The mean cell volume was calculated to be 958 cu mu. The mitochondrial volume density value averaged 59% of the cytoplasmic volume, and the mean nuclear volume density was 24% of the cell volume. These findings are compared with previous quantitative electron microscopic data on various epithelial cells from the digestive system, including the salivary glands.

In adenoid cystic carcinoma (ACC) of salivary gland origin, intermediate filaments of tumour cells were investigated by immunohistochemical techniques and complex carbohydrates within the pseudocysts by ultrastructural methods. The intermediate filament proteins vimentin and cytokeratin were found in most neoplastic cells. The pseudocysts of the tumours were found to contain proteoglycan particles stainable after glutaraldehyde fixation--but not after osmium fixation alone. Ruthenium red (cationic dye) enhanced the staining whereas periodic acid-chromic acid-silver methenamine staining or phosphotungstic acid staining did not visualize the proteoglycan particles mainly containing acid proteoglycans which are normally produced by mesenchymal tissue. The cells of adenoid cystic carcinoma thus have an intermediate filament content and produce complex carbohydrates characteristic of both epithelial and mesenchymal tissue. Hence, an origin in an undifferentiated pluripotential cell seems plausible.

In this experimental study performed on the rat middle ear either the Eustachian tube or the tympanic isthmus was blocked via the tympanic bulla with a polyethylene plug or a piece of Gelfoam, respectively. Effusion material was immediately observed in the attic space and subsequently the pars flaccida was drawn in a medial direction to form a retraction pocket. The initial changes in the pars flaccida structure were a degranulation of the mast cells and concomitantly metaplasia of the mucosal epithelium into cells displaying numerous osmiophilic inclusions, vacuoles and multivesicular bodies. It cannot be excluded that the initial cause of the effusion production is the histamine released from mast cell granules.

1. The effects of dopamine, 5-hydroxydopamine (5-OHDA) and noradrenaline on amylase secretion from the guinea-pig submandibular gland were investigated under in vitro conditions. 2. All three amines greatly enhanced amylase secretion. Blockade of dopamine beta-hydroxylase did not inhibit the response to dopamine. 3. Noradrenaline and dopamine stimulated amylase release from salivary glands of reserpine-treated animals, whereas 5-OHDA had no stimulatory effect on secretion in guinea-pigs pretreated with reserpine. 4. Haloperidol completely inhibited dopamine-induced enzyme discharge, but did not affect noradrenaline-initiated secretion. 5. Apomorphine caused a slight enzyme release by itself; it diminished the dopamine secretory effect, but did not modify that of noradrenaline. 6. Pimozide and fluspirilene attenuated the dopamine-induced enzyme discharge, but compared with haloperidol they were less effective. 7. It is concluded that dopamine exerts a secretagogic action different from that of noradrenaline. The possible presence of a specific dopamine receptor in salivary glands is discussed.

The ultrastructure and cytochemistry of the secretory granules of the male hamster submandibular salivary gland were studied; After fixation in glutaraldehyde followed by osmium tetroxide the granules exhibit a characteristic bipartite substructure, with an electron lucid crescenteric rim and a more dense central core. A differentiation into two regions of the granules could also be visualized in specimens primarily fixed in Millonig's osmium tetroxide or in potassium permanganate. The electron lucid peripheral portion of the membrane bounded secretory granules further displays a strong positive reaction after staining of ultrathin sections with the periodic acid-chromic acid-(PA-CrA)-silver technique. The strong periodate reactivity of the rim relative to the core, suggests a difference in mucin composition of the two granule regions. With the PA-CrA-silver straining technique a positive reaction was also observed within the Golgi apparatus of the acinar cells.

The present in vitro investigation was undertaken in an attempt to obtain further information on beta-adrenoceptor specificity and action in the rat parotid gland, with regard to amylase secretion. The beta 1-selective agonist prenalterol was roughly 800 times more potent than the beta 2-agonist terbutaline, and about 5 times more effective than noradrenaline in evoking amylase release . Propranolol was the most effective inhibitor of amylase release in all experiments. The beta 1-selective antagonist metoprolol and H104 /08 were also effective blockers of maximal noradrenaline- and prenalterol-induced release. The inhibition curves displayed biphasic shapes when amylase secretion was induced by noradrenaline, but not when prenalterol was the secretagogue. The beta 2-antagonist H35 /25 was without effect on maximal noradrenaline- and prenalterol-stimulated secretion. The amylase release evoked by submaximal concentration of terbutaline was inhibited by the two antagonists H35/25 and IPS 339. In another series of experiments propranolol and metoprolol clearly shifted the noradrenaline concentration-response curve to the right, whereas H35/25 was without effect. The results further demonstrate the major importance of the beta 1-adrenoceptor (noradrenaline-activated) in eliciting amylase release from the rat parotid gland. However, it is also suggested that the beta 2-adrenoceptors (terbutaline-activated) may to some extent serve the same function.

Sympathetic denervation of the rat parotid gland was performed neonatally or in adult fully developed animals on one side. The contralateral gland served as control. Two and 9 weeks later the glands were used for in vitro amylase secretory studies. The neonatally denervated glands displayed an enhanced response to high concentrations of noradrenaline, without significant changes in the lower concentration range. In adult sympathectomized animals no significant alteration could be recorded in secretory response 9 weeks after denervation. Two weeks after adult ganglionectomy a striking leftward shift of the noradrenaline concentration-response curve was observed without changes in the maximal response. Thus, the modality of the supersensitivity appears to be influenced by the age of the animal when the surgical procedure is performed, as well as by the duration of the denervation.