Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasoactive intestinal peptide (VIP), a neuropeptide coupled with adenylate cyclase, was found to induce neurite extension of PC12h cells. Neurites appeared within 1 h after addition of VIP and extended for at least 24 h. The half-maximal concentration for the effect of VIP was 50 nM. In addition to the morphological change, VIP induced expression of VGF protein, a neuron-specific protein associated with neuronal differentiation. Western blotting with anti-phosphotyrosine antibody showed that VIP stimulated tyrosine phosphorylation of two proteins of 42 and 44 kDa, which may be two isoforms of MAP kinase, erk1 and erk2. Activation of MAP kinases was confirmed by ion-exchange chromatography on a Mono Q column, from which VIP-induced kinase activity was co-eluted with MAP kinase-immunoreactivity. Tyrosine-phosphorylation of MAP kinases was also stimulated by forskolin or dibutyryl cAMP, indicating that activation of MAP kinases by VIP might be mediated by cAMP. These results suggest that VIP-induced differentiation of PC12 cells is associated with cAMP-dependent activation of MAP kinases.
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PMID:Vasoactive intestinal peptide induces differentiation and MAP kinase activation in PC12h cells. 820 80

The pharmacological properties of the pituitary adenylate cyclase activating peptides (PACAPs) and vasoactive intestinal peptide (VIP) were compared using: (i) relaxation of vascular and gastric smooth muscle in vitro, and (ii) radioligand binding to membrane preparations of a variety of tissues. Vasoactive intestinal peptide and PACAP-27 were similarly potent in relaxing rat mesenteric arteries, porcine coronary arteries, and rat gastric smooth muscle, whereas PACAP-38 was either more or less potent than the other two peptides depending on the tissue model. Cross-desensitization to relaxation and radioligand binding studies of porcine coronary arteries suggested that VIP and the PACAPs interact with a common receptor in this tissue. A PACAP-preferring receptor with low affinity for VIP was identified in radioligand binding studies of rat brain and anterior pituitary. A second, nonselective, receptor that binds VIP and both PACAPs with high affinity was observed in preparations of rat and porcine arteries and rat lung, liver, brain, and anterior pituitary.
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PMID:Comparative study of vascular relaxation and receptor binding by PACAP and VIP. 823 21

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are hypothalamic peptides sharing considerable sequence homology which are postulated to be hypophysiotrophic releasing factors. When infused into man, PACAP has no effect on anterior pituitary hormone levels, while VIP causes a significant increase in circulating prolactin concentrations. However, PACAP has recently been shown to augment the release of LH and FSH in response to LHRH in rat anterior pituitary cell culture. In order to ascertain if either peptide has a similar effect in man, PACAP and VIP were infused at 3.6 pmol/kg per min into six healthy male volunteers, and an LHRH test was performed 30 min after the infusion was commenced. Infusion of PACAP did not alter the gonadotrophin response to LHRH significantly. However, VIP augmented the release of LH significantly, both during the infusion and for 30 min thereafter, although there was no effect on FSH release. Thus VIP, but not PACAP, potentiates the release of LH after LHRH injection in man.
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PMID:Vasoactive intestinal peptide, but not pituitary adenylate cyclase-activating peptide, modulates the responsiveness of the gonadotroph to LHRH in man. 837 Oct 83

Vasoactive intestinal peptide (VIP) receptors were characterized in epithelial plasma membranes from human small intestine. Native VIP inhibited the binding of 125I-labeled VIP to jejunal membranes, and Scatchard analysis of these data was consistent with the existence of one class of receptor with a dissociation constant of 42 pM and a maximal binding of 256 fmol/mg membrane protein. VIP stimulated adenylyl cyclase activity in human jejunal membranes in the 0.01 nM-1 microM range [half-maximal effective dose = 0.7 nM]. Coupling of VIP receptors with a Gs protein was further assessed by the ability of GTP (10(-8) to 10(-3) M) to inhibit 125I-VIP binding to membranes. 125I-VIP binding was seven to eight times higher in villus cells than in crypt cells. Finally, 125I-VIP binding was detectable throughout the small and large intestines with the highest binding in jejunum. Among the natural peptides structurally related to VIP, some inhibited 125I-VIP binding with the following order of potency: VIP = pituitary adenylate cyclase-activating peptide (PACAP)-27 = PACAP-38 > helodermin >> peptide histidine methionineamide = human growth hormone-releasing factor > secretin. The same order of potency of peptides for inhibiting 125I-VIP or 125I-labeled PACAP was observed, supporting that the two tracers bound to a common VIP-PACAP receptor site. This order of potency was also observed for the stimulation of adenylyl cyclase activity by these peptides. 125I-VIP was cross-linked to membranes using disuccinimidyl suberate. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, one single band of 70,000 mol wt was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of a common VIP-PACAP receptor in human small intestinal epithelium. 838 39

Ductal elements within salivary glands are responsible for modifying the electrolyte composition of primary saliva secreted by the acini. To study the mechanism and regulation of the transport processes involved requires a suitable preparation of functional ducts. To this end we have isolated intralobular ducts from rabbit mandibular salivary glands using the technique of tissue dissociation and microdissection. Light and electron microscopy demonstrated that the ducts corresponded ultrastructurally to striated intralobular ducts of the intact gland. Ducts could be maintained in tissue culture on polycarbonate filter rafts for up to 36 h, during which time the ends of the ducts did not usually seal. The overall resting content of ductal adenosine 3',5'-cyclic monophosphate (cyclic AMP) was 16.0 +/- 3.0 fmol mm-1 and increased dose dependently in response to stimulation with the beta-adrenoceptor agonist isoprenaline (10(-9)-10(-4) M; concentration required to produce a half-maximal response, K0.5 = 2.1 x 10(-6) M). The response to isoprenaline was blocked by the antagonist propranolol. Intracellular cyclic AMP content was also raised by the adenylate cyclase activator forskolin and by prostaglandin E2. Acetylcholine (3 x 10(-8)-10(-5) M) caused a dose-dependent and maintained rise in [Ca2+]i (K0.5 = 2.5 x 10(-7) M). This increase in [Ca2+]i could be reversed by the muscarinic antagonist atropine and appeared to result from a combination of mobilization of intracellular Ca2+ stores and entry of Ca2+ from the extracellular fluid. Noradrenaline induced only a very small, mainly transient rise in [Ca2+]i while phenylephrine failed to increase [Ca2+]i at all. Vasoactive intestinal peptide (5 x 10(-7) M) also produced a marginal, maintained rise in [Ca2+]i. Substance P, bombesin, isoprenaline, and prostaglandin E2 did not elevate [Ca2+]i. Application of the calcium ionophore ionomycin induced a substantial maintained rise in [Ca2+]i. Taken together, these results indicate that isolated and cultured striated ducts (i) possess intact beta-adrenoceptors coupled to adenylate cyclase, putative receptors for prostaglandin E2 and muscarinic receptors, and (ii) represent a viable preparation for the study of the transport mechanisms involved in the ductal modification of salivary fluid composition.
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PMID:Structural and functional characterization of striated ducts isolated from the rabbit mandibular salivary gland. 838 3

The binding of ovine pituitary adenylate cyclase-activating peptide (PACAP-38) to rat lung membranes was investigated using [125I]PACAP-38 as radioligand. Binding was rapid at 37 degrees C, reversible, saturable, and time, concentration, and temperature dependent. Kinetic parameters derived from saturation experiments revealed a Kd = 100 +/- 15 pM, Bmax = 310 +/- 36 fmol/mg protein, and a Hill slope factor (nH) of 1.17 +/- 0.12. Various chemically synthesized analogues of PACAP-38, as well as related peptides, were tested for their ability to displace [125I]PACAP-38. Of those that had an IC50 < 0.2 microM, the following order of potency was determined: PACAP-38 (IC50 = 25 nM) > or = [Ile2]PACAP-38 (IC50 = 31 nM) > PACAP-27 (IC50 = 54 nM) > [Tyr1]PACAP-38 (IC50 = 104 nM) > GHRH(1-29)NH2 (IC50 = 108 nM) > PHI (IC50 = 181 nM) > [Ser2]PACAP(2-38) (IC50 = 198 nM). Glucagon, PHM, secretin, and GIP exhibited little affinity in the same binding assay. Vasoactive intestinal peptide (VIP) had an IC50 in excess of 1 microM. When [125I]VIP was used as radioligand, PACAP-27 had an IC50 = 0.2 nM > PACAP-38 (IC50 = 0.5 nM) > VIP (IC50 = 16 nM). A novel analog of PACAP-38, [4-Cl-D-Phe6,Leu17]PACAP-38, was able to displace [125I]VIP very efficiently (IC50 = 1 nM), but had little potency in displacing [125I]PACAP-38 (IC50 = 320 nM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction of ovine pituitary adenylate cyclase-activating peptide (PACAP-38) with rat lung membranes. 839 24

Vasoactive intestinal peptide (VIP) is a putative neurotransmitter found in extrinsic and intrinsic nerves of the heart. VIP can be released by vagal stimulation but, contrary to ACh, causes positive chronotropic effects as a result of binding to cardiac receptors which stimulate adenylate cyclase, and thus has been implicated in vagal tachycardias. Since the rate of diastolic depolarization of sinoatrial (SA) node myocytes depends on the hyperpolarization-activated current (if), which is directly activated by cytoplasmic cAMP, we studied the action of VIP on if in myocytes isolated from the SA node of the rabbit. VIP (0.65 microM) reversibly increased if at -65 mV but had no effect at -115 mV suggesting that its primary effect was to shift the activation curve to more positive voltages. Hyperpolarizing ramp and voltage compensation protocols indicated that VIP shifts the activation curve of if by approximately 5-6 mV in the positive direction with no change in maximal conductance. This shift may be the mechanism by which VIP produces its positive chronotropic effect and supports a negative feedback role for this peptide during elevated vagal activity.
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PMID:Activation of the hyperpolarization-activated current (if) in sino-atrial node myocytes of the rabbit by vasoactive intestinal peptide. 859 36

Vasoactive intestinal peptide (VIP) has been considered as an autocrine growth factor in neuroblastomas. Pituitary adenylate cyclase activating polypeptides (PACAPs) are newly recognized members of the VIP family of neurohormones. As compared to VIP, PACAP has been reported to be biologically more potent and more efficient in tissues expressing selective PACAP receptors rather than common VIP/PACAP receptors. PACAPs and VIP interact with the same affinity and stimulate adenylate cyclase activity with the same efficacy and potency on the VIP receptors, but PACAPs act also on a more selective PACAP receptor that also recognizes VIP but with a 100- to 1,000-fold lower affinity. Thus, depending on the type of receptors expressed at a cell surface, PACAP may be more potent and efficient than VIP. The capacity of 22 surgical specimens of neuroblastomas and of 5 established cell lines to synthesize PACAP and VIP and to synthesize and express PACAP receptors and VIP receptors was studied. Using the reverse transcriptase-polymerase chain (RT-PCR) method with specific primers, we detected the mRNAs coding for PACAP and VIP in 19 and 3 out of 22 samples, respectively. PACAP mRNA was expressed in 3 of the 5 cell lines studied and VIP mRNA in 4. Using the same techniques, PACAP and VIP receptors mRNA were detected in 21, and 13 of the 22 tumor samples and in 5 and 1 of the cell lines studied, respectively. The expression of the PACAP receptor was demonstrated by direct binding studies and/or by the relative potency of PACAPs and VIP to stimulate adenylate cyclase activity in 16 of the 22 tumors and in all the cell lines. In addition, there was no correlation between tumor stage and the expression of mRNA coding for the peptides and the receptors. The present results demonstrated that PACAP could also be a candidate as an autocrine regulator of neuroblastoma which a higher activity than VIP.
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PMID:Pituitary adenylate cyclase activating peptide and its receptors are expressed in human neuroblastomas. 869 38

Vasoactive intestinal peptide (VIP) is an important member of the group of neuropeptides that appears to be involved in the regulation of prostatic growth and function. Here we studied VIP receptors in membranes from human benign hyperplastic prostate. Accordingly to observations in rat prostatic membranes, [125I]VIP binding to human prostatic membranes suggested two classes of binding sites with high Kd = 0.22 nM) and low (Kd = 37.7 nM) affinities. VIP bound in human and rat membrane preparations to a common VIP/pituitary adenylate cyclase-activating peptide (PACAP) receptor, as VIP, PACAP-27, and PACAP-38 were equipotent for competition of [125I]VIP binding. A PACAP-preferring receptor appears to be expressed in human prostate, since [125I]PACAP binding was displaced with more potency by PACAP than by VIP, and a messenger RNA corresponding to type I PACAP receptor was found. Cross-linking experiments suggested a VIP receptor of about 71 kDa in human and 52 kDa in rat prostates. The binding of [125I]VIP to membranes and the labeling of the bands observed after electrophoresis were competitively inhibited by GTP, suggesting the coupling of VIP receptors to a G protein. Moreover, after solubilization and cross-linking, we observed a 120-kDa band that corresponded to the VIP receptor-alpha s association. VIP stimulated adenylyl cyclase activity in a dose-dependent manner, but the potency and/or the efficacy of VIP were lower in all human preparations studied than in rat prostatic membranes. In conclusion, this study clearly demonstrates the expression of VIP/PACAP common receptors associated with alpha s protein in human prostate and suggests that these neuropeptides could play an important and complex role in the physiology and pathophysiology of this human gland.
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PMID:Characterization of vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptors in human benign hyperplastic prostate. 877 Sep 2

Vasoactive intestinal peptide (VIP) belongs to an ever growing family of neuropeptides with immunomodulatory functions. VIP-containing nerve fibers are present in both primary and secondary lymphoid organs, frequently in close proximity to immune cells. In addition, several types of immune cells, including T lymphocytes may function as local VIP sources in the lymphoid microenvironment. VIP released from neuronal and/or non neuronal sources exerts immunomodulatory effects through direct binding to VIP receptors (VIP-Rs), which are expressed on most immune cells. The existence of lymphocytic VIP-Rs has been demonstrated initially through binding studies, and more recently, through molecular biology technology. Both VIP-R1 and VIP-R2, which express high affinity for VIP and related neuropeptides such as the pituitary adenylate cyclase activating peptide (PACAP), are present on lymphocyte subsets, and recent reports suggest that whereas VIP-R1 is expressed constitutively, VIP-R2 expression is induced upon lymphocyte activation. Although VIP affects a variety of immune functions, its primary immunomodulatory function seems to be anti-inflammatory in nature. Whereas a rapid inflammatory response is essential for the ultimate elimination of foreign antigens, its intensity and duration have to be strictly controlled to avoid extensive tissue damage. In this respect, neuropeptides with anti-inflammatory functions such as VIP or the structurally related PACAP, timely released within the lymphoid organs, could play an important physiological role in the down-regulation of the immune response. Cytokines, soluble products of immune cells, play major roles in lymphocyte development, activation, and differentiation. As most cytokines are functionally pleiotropic, redundant, and interdependent, local interactions within the cytokine-neuroendocrine network have significant impact on cytokine production and function. Therefore, the immunomodulatory activities of VIP could be mediated, at least partially, through effects on the production of cytokines. The purpose of this article is to review the existing information regarding the VIP modulation of cytokine expression in immune cells. Both VIP and PACAP downregulate the expression of IL-2 mRNA and protein in T cells activated through the T cell receptor, through reducing both the stability and the de novo transcriptional rate of the IL-2 message. Reduction in the amount of IL-2 generated by the activated CD4+ T cells impacts on both T cell proliferation and on further sequential cytokine production. This is indeed the case with IL-4, which is affected by VIP indirectly, through inhibition of IL-2. In contrast, the inhibitory effect of VIP and PACAP on IL-10 production proceeds through a direct transcriptional event. In contrast to IL-2 which functions solely as a proinflammatory cytokine, IL-4 and IL-10 act as pro- or anti-inflammatory cytokines, depending on their involvement in specific immune responses. Therefore, depending on interactions with the local cytokine network, VIP and related neuropeptides may contribute significantly to controlling the amplitude and timing of the inflammatory response to foreign antigens. Although the role of VIP and related peptides on T cell development has not been investigated yet, the presence of VIP and VIP-Rs in the thymus, and their effect on thymic cytokine production, suggests that VIP and/or PACAP released locally within the thymic environment could also affect T cell development, and therefore participate in the generation and maturation of immune cells.
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PMID:Regulatory effects of vasoactive intestinal peptide on cytokine production in central and peripheral lymphoid organs. 879 Jul 82


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