Search

The sialogogic response of submandibular glands to analogs of the C-terminal hexapeptide of substance P with various amino acids at the N-terminus was investigated in urethane-anesthetized rats. The rank order of potencies was as follows: SP greater than (pGlu6)SP6-11 much greater than (Dab6)SP6-11 greater than (Orn6)SP6-11 greater than (Gln6)SP6-11 greater than (Lys6)SP6-11 much greater than (Ala6)SP6-11. These results suggest that the sialogogic activity of the analogs of the C-terminal hexapeptide is influenced by the steric effects of the N-terminal amino acid, and the nature of its side chain is of particular importance.

The actions of dobutamine (DOB) and terbutaline (TER) on the secretion of marker glycoprotein (GP) from the secretory cells of the glands and secretion of fluid from rat submandibular gland (SMG) were investigated in combination with two antagonists, metoprolol (MET) and ICI-118551 (ICI). The ED50 value of fluid secretion was 8.7 mg/kg for DOB and 5.9 mg/kg for TER. MET, administered prior to either agonists at a dose of 40 mg/kg, inhibited the fluid secretion. However, the blocking effects of ICI were considerably lower than those of MET. The electrophoretic profiles of GP in DOB-evoked saliva were similar to those in TER-evoked saliva, and included two characteristic main bands of GP I (130 KDa) and GP IV (21.5 KDa) from the acinar cells and a minor band of GP III (31 KDa) which originated in the cells of the granular tubules. When MET was administered at a dose of 5 mg/kg prior to DOB, the intensity of band I decreased, whereas that of band III did not change. These results showed that the SMG of rats contains both beta 1- and beta 2-adrenoceptors and that beta-receptors which mediate the secretion of GP from the acinus and fluid from the gland are mainly of the beta 1-subtype.

The action of dopamine (DA) on salivation and the secretion of marker glycoproteins (GP) from secretory cells of the rat submandibular gland (SMG) was investigated using various blockers at doses of 1 or 2 mg/kg (i.v.). DA at doses from 5 to 40 mg/kg (i.p.) dose-dependently increased salivation and the concentration of protein in SMG saliva. The order of inhibitory potency on salivation was propranolol (PPR) greater than phentolamine (PHN) much greater than haloperidol (HAL) when DA was administered i.p. at a dose of 10 mg/kg and PHN much greater than HAL much greater than PPR when the dose of DA was 40 mg/kg. The concentration of protein in saliva after pretreatment with HAL or PHN increased significantly at a dose of 40 mg/kg of DA, but did not increase at a dose of 10 mg/kg of DA. Moreover, pretreatment with PPR decreased it at both doses of DA. The electrophoretic profiles of GP in DA-evoked saliva showed two characteristic main bands of GP I (130 KDa) and GP IV (21.5 KDa) contained in the acinar cells (AC) and a minor band of GP III (31 KDa) which originated from the granular tubular cells (GT). The profile was not changed by pretreatment with PHN and HAL when DA was administered at a dose of 10 mg/kg, but at a dose of 40 mg/kg, the intensity of band I increased. Pretreatment with PPR, when DA was administered at 40 mg/kg, caused an increase in the intensity of band III and a reduction in that of band I. These results suggest that DA, at low doses, affects the AC, whereas at a higher dose, it affects both the AC and GT.

The actions of four choline esters, acetylcholine (ACH), methacholine (MET), carbachol (CAR) and bethanechol (BET), on the secretion of saliva and the specific glycoprotein (GP) contained in the secretory cells of the submandibular gland (SMG) of the rat were compared under conditions with and without physostigmine (PHY). The ED50 values with respect to salivation were 17 mg/kg for ACH, 1060 micrograms/kg for BET, 810 micrograms/kg for MET and 75 micrograms/kg for CAR, whereas after pretreatment with PHY, ED50 values were lowered to 7.5 mg/kg for ACH and 212 micrograms/kg for MET, but remained unchanged for CAR and BET. SDS-polyacrylamide gel electrophoresis demonstrated that the saliva from the SMG elicited by the four choline esters contained GP I (130 KDa) and GP IV (21.5 KDa), characteristic of the acinus, and a band of GP III (31 KDa), which originates from the granular tubules. The order of intensity of these bands was band I much greater than band III = band IV. Among these bands, band I increased in intensity in a dose-dependent manner. These results suggest that the four choline esters act mainly on the acinar cells, but exert some effects on the granular tubules of the rat SMG.

The effects of substance P, neurokinin A, physalamine, and eledoisin on the secretion of fluid and glycoproteins from the submandibular glands of various rodents were investigated. Following i.v. injection of each peptide at a dose of 20 micrograms/kg, the major glycoprotein species secreted from rats and guinea pigs were shown to be electrophoretically identical with those found in the acini. However, saliva was not elicited from the mice and hamsters. These results suggest that in both rats and guinea pigs, tachykinins act on the acinar cells of the submandibular gland only.

The actions of metaraminol on the secretion of fluid and glycoproteins from rat submandibular glands were investigated using phentolamine, propranolol and reserpine. Metaraminol at doses from 1 to 8 mg/kg (i.p.) increased the salivation and the amounts of protein in submandibular saliva in a dose-dependent manner. The salivation induced by metaraminol at 2 mg/kg was inhibited strongly by pretreatment with propranolol, whereas the salivation induced by metaraminol at 8 mg/kg was inhibited strongly by phentolamine. Reserpine inhibited the secretion of fluid caused by both doses of metaraminol. The electrophoretic profiles of saliva evoked by metaraminol at 2 mg/kg revealed two main bands of glycoprotein, I and IV, which originated from the acinus, and the intensities of these bands were decreased by treatment with propranolol, whereas the major band in saliva induced by 8 mg/kg of metaraminol was glycoprotein III, which originated from the granular tubules. The intensity of band III was decreased by pretreatment with phentolamine. These results suggest that metaraminol, at small doses, stimulates mainly the beta-adrenoceptor in the acinus, whereas at large doses, it prominently stimulates the alpha-adrenoceptors in the granular tubules, although metaraminol at small and large doses is able to stimulate alpha- and beta-adrenoceptors in rat submandibular gland.

The action of substance P on glycoprotein secretion from acinar cells of the rat submandibular gland was described in this report. Salivation elicited by i.v. injection of 0.5 to 20 micrograms/kg of substance P was increased dose-dependently, and its flow rate was highest at the first 1 min. Major glycoprotein species secreted into saliva by substance P-stimulus were shown to be electrophoretically identical with those found in acini, but not granular convoluted tubules. These results support the view that substance P acts on acinar cells of the submandibular gland and stimulates secretion of saliva from the cells.