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AIM To investigate the role of vasoactive intestinal peptide (VIP) in form-deprivation myopia (FDM). METHODS FDM was created in three groups of eight chicks by placing a translucent diffuser on their right eyes. Intravitreal injections of saline and VIP were applied once a day into the occluded eyes of groups 2 and 3, respectively. Retinoscopy and axial length (AL) measurements were performed on the first and 8th days of diffuser wear. The retina mRNA levels of the VIP receptors and the ZENK protein in right eyes of the three groups and left eyes of the first group on day 8 were determined using real time polymerase chain reaction (PCR). RESULTS The median final refraction (D) in right eyes were -13.75 (-16.00, -12.00), -11.50 (-12.50, -7.50), and -1.50 (-4.75, -0.75) in groups 1, 2, and 3, respectively (P

Vasoactive intestinal peptide (VIP) plays important roles in many biological functions, such as, stimulation of contractility in the heart, vasodilation, promoting neuroendocrine-immune communication, lowering arterial blood pressure, and anti-inflammatory and immune-modulatory activity. Osteoarthritis (OA) is a chronic and degenerative bone disease, which is one of the most common causes of disability and most common in both sexes as people become older. Interestingly VIP can prevent chronic cartilage damage and joint remodeling. This review article provides update information on the association of VIP and OA and its treatment. Evidences suggest that VIP is down-regulated in synovial fluid of OA, and VIP down-regulation leads to increase in the production of pro-inflammatory cytokines that might contribute to the pathogenesis of OA; however contradictory reports also exist suggesting that accumulation of VIP in joints can also contribute OA. A number of studies indicated that up-regulation of VIP can counteract the action of pro-inflammatory stimuli and alleviate the pain in OA. More clinical investigations are necessary to determine the biology of VIP and its therapeutic potential in OA that might represent the future standards of care for OA.

Vasoactive intestinal peptide (VIP) is a 28-amino acid polypeptide first isolated from swine duodenum. VIP is a neurotransmitter that is extensively distributed in tissues. According to published reports, VPAC1 and VPAC2 act as VIP receptors and are widely present in the central nervous system and peripheral tissues. VIP exerts diverse actions on the cardiovascular system, pancreas, digestive tract, respiratory system, and urological system. Recent reports indicated that VIP has immunological and neuroprotective effects and also affects cell growth. While primary investigations for developing therapeutic applications for various pathological conditions and diseases are underway, the structure and function of VIP should be analyzed in more detail.

We have studied the developmental patterns of vasoactive intestinal polypeptide (VIP) binding sites in the human hypothalamus. VIP recognition sites were widely distributed throughout the rostrocaudal extent of the hypothalamus. VIP binding was generally low in the fetal and neonatal periods and a tendency in increasing densities was observed during postnatal development. The age comparison of binding density indicates variations in several structures. Thus, the densities were higher in older infants in the preoptic area, lamina terminalis, and infundibular (IN) nucleus. These differences suggest the implication of VIP receptors in the development of this brain structure and the maintenance of its various functions.

VIP receptors were investigated in breast cancer biopsy specimens. Twenty biopsy specimens bound 125 I-VIP with high affinity. Also, each of the 20 biopsy specimens had high amounts of VPAC1 receptor mRNA. MCF-7 cells have VPAC1 receptors that bound the VIP chemotherapeutic conjugate, (Ala 2,8,9,19,24,25,27 Nle 17 , Lys 28 )VIP-L2-camptothecin, with high affinity. VIP chemotherapeutic conjugates may be useful agents to inhibit the growth of breast cancer.

Moody, T. W., J. Leyton, E. Unsworth, C. John, L. Lang and W. C. Eckelman. (Arg 15 , Arg 21 ) VIP: Evaluation of biological activity and localization to breast cancer tumors. Peptides 19 (3) 585–592, 1998.—VIP analogs, which contain a single lysine amino acid, were synthesized and evaluated using breast cancer cells. (Arg 15 , Arg 20 ) VIP, (Arg 15 , Arg 21 ) VIP, and (Arg 20 , Arg 21 ) VIP inhibited 125 I-VIP binding to T47D cells with high affinity (IC 50 values of 1.2, 1.0, and 0.8 nM, respectively). The VIP analogs elevated cAMP in T47D cells with ED 50 values ranging from 0.1–1 nM. Because (Arg 15 , Arg 21 ) VIP was the most potent at elevating cAMP, it was characterized further. (Arg 15 , Arg 21 ) VIP transiently increased c -fos gene expression in breast cancer cells. N -Succinimidyl-4- 18 F (fluoromethly) benzoate was prepared in one chemical step from N -succinimidyl-4-(4-nitrobenzenesulfonyl)oxomethyl)benzoate by adding 18 F in acetone at room temperature. This prosthetic group was then reacted with (Arg 15 , Arg 21 ) VIP ((RR) VIP). ( 18 F-RR) VIP bound with high affinity to T47D cells and was rapidly internalized. ( 18 F-RR) VIP was injected intravenously into nude mice bearing breast cancer xenografts and after 4 h, the density of ( 18 F-RR) VIP was elevated in the tumors relative to normal organs. These data suggest that VIP receptors may be used to localize breast cancer tumors.

Vasoactive intestinal peptide (VIP) plays diverse and important role in human physiology and physiopathology and their receptors constitute potential targets for the treatment of several diseases such as neurodegenerative disorder, asthma, diabetes, and inflammatory diseases. This article reviews the current knowledge regarding the two VIP receptors, VPAC(1) and VPAC(2), with respect to mechanisms involved in receptor activation, G protein coupling, signaling, regulation, and oligomerization., Journal Article, SCOPUS: re.j, info:eu-repo/semantics/published

The effect of ovine prolactin (oPRL) administration to laying and incubating turkey hens was studied. In experiment one, five treatment groups (n = 6) of laying hens received injections of vehicle or oPRL (4 mg/bird/day) for 2, 4, 8, or 14 days. Hypothalamic vasoactive intestinal peptide (VIP) content decreased to its lowest level (p < 0.05) by Day 2 of oPRL injection. Serum turkey PRL decreased by Day 8 of injection, reaching nadir by Day 14. Similar to the decline in hypothalamic VIP content, the maximal decline in the number of anterior pituitary VIP binding sites was achieved by Day 2 of oPRL administration. Hypothalamic GnRH-I content decreased after 2 days of oPRL injection and remained low through Day 14 of the experiment. GnRH-II levels declined with time, reaching significantly lower levels after 8 days of injections, and remained low through Day 14. Plasma LH levels also declined (p < 0.05) after Day 14 of oPRL administration. In experiment 2, two groups (n = 6) of incubating birds were used: controls receiving injections of vehicle only and birds receiving injections of oPRL (4 mg/bird/day) for 10 days. Exogenous oPRL had no effect on hypothalamic VIP, GnRH-I or II, anterior pituitary VIP binding sites, or plasma turkey PRL or LH. The findings suggest that in laying hens, PRL inhibits its own secretion by acting on both the hypothalamus and the anterior pituitary; this phenomenon does not occur in incubating birds. Furthermore, we provide evidence that pRL acts centrally to reduce LH levels by reducing GnRH levels in the hypothalamus.

In early reports on 125 I-VIP binding experiments in liver membranes, it has been proposed that, the VIP binding sites were partially sensitive to GTP. Here we confirm that the VIP binding sites of chicken liver membranes consisted mainly in bivalent VIP/PACAP receptors and that about 50% of the 125 I-VIP binding capacity was not affected by the GTP analogue GppNHp. Part of these bivalent receptors also appeared to represent PHI binding sites. In GppNHp-treated membranes, the GTP-insensitive VIP binding sites displayed a 17-fold higher relative affinity than in control membranes for the VIP analogue PHI. Such data suggested that GTP-insensitive VIP receptors may correspond to a subclass of high-affinity PHI receptors. Cross-linking of 125 I-VIP or 125 I-PHI to their receptors, revealed 2 components of 48 and 60kDa. The radiolabelling of the 60kDa component was strongly affected by increasing concentrations of the GTP analogue but was modestly abolished by an excess of PHI. Conversely, the radiolabelling of the 48kDa molecular form was not affected by the GTP analogue but was efficiently abolished by increasing concentrations of PHI. Taken together, the data suggest that the 48kDa component expressed in chicken liver membranes display the properties of a GTP-insensitive VIP/PHI receptor that can be pharmacologically discriminated from the GTP-sensitive 60kDa form, through its much higher affinity for PHI.

Pancreatic acini from most species possess vasoactive intestinal peptide (VIP) receptors. Recently, two subtypes of VIP receptors, VIP1-R and VIP2-R, were cloned. Which subtype exists on pancreatic acini or mediates secretion is unclear. To address this, we examined pancreatic acini from both rat and guinea pig. VIP1-R and VIP2-R mRNA were identified in dispersed acini from both species by Northern blot analysis and in rat by Southern blot analysis. With the use of the VIP2-R-selective ligand Ro-25-1553 in both species, inhibition of binding of125I-labeled VIP to acini showed a biphasic pattern with a high-affinity component (10%) and a second representing 90%. The VIP1-R-selective ligand, [Lys15,Arg16,Leu27]VIP-(1—7)-GRF-(8—27), gave a monophasic pattern. Binding of Ro-25-1553 was better fit by a two-site model. In both rat and guinea pig acini, the dose-response curve of Ro-25-1553 for stimulation of enzyme secretion was biphasic, with a high-affinity component of 10–15% of the maximal secretion and a low-affinity component accounting for 85–90%. At low concentrations (10 nM) of Ro-25-1553 and [Lys15,Arg16,Leu27]VIP-(1—7)-GRF(8—27), which only occupy VIP receptors, a 4-fold and a 56-fold increase in cAMP occurred, respectively. These results show that both VIP1-R and VIP2-R subtypes exist on pancreatic acini of rat and guinea pig, their activation stimulates enzyme secretion by a cAMP-mediated mechanism, and the effects of VIP are mediated 90% by activation of VIP1-R and 10% by VIP2-R. Because VIP has a high affinity for both VIP-R subtypes, its effect on pancreatic acini is mediated by two receptor subtypes, which will need to be considered in future studies of the action of VIP in the pancreas.

VIP-containing cells in the neocortex are intrinsic neurons of the bipolar type, which release VIP through mechanisms that involve Ca2+ and lipoxygenase metabolites. VIP receptors are coupled to cAMP-generating systems that are amplified by various neurotransmitters such as noradrenaline, histamine and GABA. Pierre Magistretti reviews the evidence that VIP neurons play an important role in the local regulation of metabolism in the cerebral cortex by stimulating glycogenolysis and altering cortical blood flow.

Acquired immunodeficiency syndrome (AIDS) is initiated by the attachment of the human immunodeficiency virus (HIV) to specific target cells. An octapeptide sequence contained within the envelope of HIV, peptide T, mediates the viral binding. Since there is a considerable structural homology between peptide T and VIP, it has been proposed that the VIP receptor may be the naturally occurring protein which provides the corresponding cellular attachment site. In three different models (rat intestinal epithelial cell membranes, rat liver plasma membranes and human colonic cells), we document the lack of interaction between peptide T and the VIP receptor. These observations would also exclude any pathophysiologic effect caused by the crossreactivity of peptide T or its analogues and these VIP receptors.

Nine VIP sequences have been tested for their ability to inhibit the specific binding of 125I-VIP and to stimulate adenylate cyclase activity in intestinal epithelial membranes from rat and man. They are VIP 2–28; VIP 1–14; VIP 2–14; VIP 14–28; VIP 15–28; VIP 20–28; VIP 21–28 and two sequences where the N-terminal VIP 1–6 or VIP 1–9 have been joined covalently with the C-terminal VIP 20–28 or VIP 21–28. It appears that only VIP 2–28, VIP 14–28 and VIP 15–18 are able to inhibit competitively the binding of 125I-VIP to human and rat membranes. These analogues are respectively 88, 8,300 and 25,000 times less potent than VIP 1–28 in rat; they are respectively 70, 7,900 and 13,000 times less potent than VIP 1–28 in man. With respect to adenylate cyclase activation, VIP 14–28 and VIP 15–28 are very weak stimulators in the membranes from both species. VIP 2–28 behaves as a full VIP agonist in man whereas it is a partial VIP agonist in rat. These results indicate the structural importance of the whole VIP sequence for interacting with human and rat VIP receptors and further argue for a different structural requirement of rat and human receptors.

In an attempt to evaluate the role of VIP in affective disorder, measurements of lymphocyte VIP receptors, and plasma and CSF VIP levels were made in unmedicated and lithium-treated euthymic bipolars and controls. Lithium decreased plasma (P=0.01) and CSF (P=0.05) VIP levels and increased the affinity (decreased the KD) of the VIP lymphocyte receptor (P

Specific binding of vasoactive intestinal peptide (VIP) and VIP-stimulated cyclic AMP accumulation were studied in small intestinal epithelial cells (both of crypt and villous levels) 3, 7 and 14 d after a 60% resection of the small intestine. The affinity, but not the binding capacity, of VIP receptors decreased during the adaptive hyperplastic response. Basal cyclic AMP levels were similar in cells of both control and resected rats. Resection induced a decrease of potency, but not of efficiency, of VIP on the stimulation of cyclic AMP accumulation.

Relaxations of the feline intrapulmonary bronchus (IPB) induced by VIP or nonadrenergic noncholinergic (NANC) inhibitory nervous stimulation were unaffected by the VIP receptor antagonist [Ac-Tyr1,D-Phe2]-GRF (1-29) (30 microM). A second VIP antagonist, [pCl-D-Phe6,Leu17]-VIP (30 microM), also had no effect on NANC relaxation responses or IPB sensitivity to VIP. However, responses to three of the four highest VIP concentrations were inhibited by this antagonist. These results indicate that [Ac-Tyr1,D-Phe2]-GRF (1-29) and [pCl-D-Phe6,Leu17]-VIP are not effective competitive antagonists of VIP receptors in feline airways and, hence, have but limited applicability in determining the role of VIP in mediating airway NANC inhibitory responses in this tissue.

Chronic atropine treatment (14 days, 20 mg × day−1 × kg−1 SC) caused a 75% increase in the number of VIP receptors in the rat cerebral cortex. The affinity of these receptors for 125I-VIP was not altered significantly by the atropine treatment. The same treatment led to a 20% decrease in VIP tissue levels. Muscarinic receptor number was also increased by 26%. The results indicate that interactions between VIP- and muscarinic receptors may be of importance in the rat cerebral cortex.

The effects of experimental uremia on the concentration of vasoactive intestinal peptide (VIP) in duodenum as well as on the interaction of this neuropeptide with the corresponding epithelial cells were studied in rats. Duodenal VIP concentration was significantly decreased in uremic rats as compared to control animals. The specific binding of VIP to duodenal epithelial cells increased in rats with uremia due to an increase in the number of VIP receptors rather than a change in the binding affinity or in the extent of VIP degradation. On the other hand, the efficacy but not the potency of VIP upon cyclic AMP generation varied in parallel to that observed at the receptor level.

In human antral membranes, VIP and its natural analogs inhibited the binding of HPLC-purified 125I-VIP, according to the following order of potency: VIP greater than rh GRF greater than helodermin greater than r PHI greater than PHM greater than p PHI greater than hp GRF greater than h, p secretin. No specific binding was detected in plasma membranes purified from the human fundus. In human antral membranes, Scatchard plots were compatible with the existence of two classes of VIP receptors, the first class with high affinity and low binding capacity (Kd = 0.1 nM, Bmax = 10 fmol/mg protein) and another class with a low affinity and higher binding capacity (Kd = 12) nM, Bmax = 1,000 fmol/mg protein). The structure of the VIP receptor in purified plasma membranes prepared from human antral glands and from the HGT-1 human gastric cancer cells was subsequently probed using the cross-linking reagent DSP and 125I-VIP. In agreement with the pharmacological study and the Scatchard analysis of the binding data, SDS gel electrophoresis of the solubilized receptor identified two radiolabeled peptides Mr 67,000 and 34,000 containing disulfide bonds. According to its sensitivity to low doses of VIP and to GTP, the Mr 67,000 binding site represents the membrane domains involved in the physiologial regulation of adenylate cyclase by VIP in normal and transformed human gastric epithelia.