Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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), secretin, and C-terminal octapeptide of cholecystokinin (CCK-8) receptors were identified in rat pancreatic plasma membranes by the ability of these peptides to stimulate adenylate cyclase activity. The membrane preparation procedure was conducted through a series of steps including discontinuous sucrose density gradient fractionation. 5 mM beta-mercaptoethanol was added stepwise. Membrane preparations obtained stepwise were preincubated for 10 min at 25 degrees C in the presence of various concentrations of beta-mercaptoethanol or dithiothreitol before assaying adenylate cyclase. The use of the reducing agents exerted no effect on p[NH]ppG-, NaF-, and CCK-8- stimulated activities. By contrast, stimulation of adenylate cyclase by low VIP concentrations was specifically altered when beta-mercaptoethanol was used during tissue homogeneization at 5 degrees C. In addition, both VIP and secretin responses were highly sensitive towards a preincubation of 10 min at 25 degrees C in the presence of dithiothreitol. These results were likely to reflect alterations at the receptor level. 125I-VIP binding was, indeed, reduced after dithiothreitol preincubation, low concentrations of the thiol reagent decreasing the apparent number of high-affinity VIP receptors and higher dithiothreitol concentrations reducing the affinity of VIP receptors.
 ...
PMID:Importance of disulfide bonds in receptors for vasoactive intestinal peptide and secretin in rat pancreatic plasma membranes. 632 86

Vasoactive intestinal peptide (VIP), a 28-amino acid peptide, plays a multifunctional neuromodulatory role in both peripheral and central nervous systems. We have recently reported that VIP induces interferon (IFN) alpha/beta synthesis in human colon adenocarcinoma cell line HT-29. It has been reported that VIP may counteract HIV-induced neuronal cell death; therefore, we postulated that the action of VIP may be mediated by a cascade regulation, involving the production of some cytokines such as IFN. Here we demonstrate that primary cultures of rat mesencephalic neurons and glial cells respond differently to VIP. Thus VIP enhanced 2'5' oligoadenylate (2'5' A) synthetase activity and inhibited vesicular stomatitis virus multiplication in glial cultures only. However, both cell cultures had functional adenylate cyclase coupled receptors for VIP. The increase in 2'5'A synthetase activity in glial cultures reached a maximum with 10(-6) M VIP and required cellular RNA and protein synthesis. Anti-IFN alpha/beta, but not anti-IFN gamma, antibodies abolished the induction of the antiviral and 2'5'A synthetase activities by VIP in rat glial-enriched cultures, suggesting that these inductions were mediated through IFN alpha/beta synthesis. Moreover, VIP or poly (i). poly (C12U) caused, in the glial cultures, the induction and secretion of an IFN of type alpha/beta with a titer value of 16 and 32 units/ml respectively. In contrast, neither of these two substances was able to induce IFN synthesis in neurons, which were, however, sensitive to IFN alpha/beta produced by VIP-treated glial cells. IFN produced by VIP in glial cells may therefore play an important role in defending the brain against viruses.
 ...
PMID:Induction by vasoactive intestinal peptide of interferon alpha/beta synthesis in glial cells but not in neurons. 750 79

Plasma membranes isolated from dispersed gastric muscle cells exhibited calmodulin-dependent NOS activity that was stimulated by Ca2+ in the range 0.1-1 mM (maximum 10 microM). Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) (in the presence of GTP), and GTP gamma S (guanosine 5'-O-(gamma-thio)triphosphate) stimulated NOS activity in a concentration-dependent fashion above that maximally stimulated by Ca2+. The increase in NOS activity induced by VIP, PACAP, and GTP gamma S was abolished by GDP beta S (guanosine 5'-O-(beta-thio)diphosphate), which had no effect on NOS activity stimulated by Ca2+. The NOS inhibitor NG-nitro-L-arginine and the calmodulin antagonist calmidazolium abolished NOS activity stimulated by all agents including Ca2+. NOS activity stimulated by GTP gamma S, VIP, and PACAP was inhibited by Gi alpha 1-2 antibody but not by Gq alpha, Gs alpha, and Gi alpha 3 antibodies. NOS activity stimulated by VIP and PACAP was inhibited by 80-83% in membranes derived from pertussis toxin-treated cells. We conclude that a Ca2+/calmodulin-dependent NOS present in plasma membranes of gastric muscle cells is activated by two homologous peptide transmitters, VIP and PACAP, via a common receptor coupled to pertussis toxin (PTx)-sensitive Gi1-2. The study provides the first evidence of receptor-mediated G protein activation of NOS in smooth muscle cells.
 ...
PMID:Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide-dependent activation of membrane-bound NO synthase in smooth muscle mediated by pertussis toxin-sensitive Gi1-2. 751 75

The innervation of the cat lower oesophagus, including the lower oesophageal sphincter, was studied by enzyme histochemistry, immunohistochemistry, and confocal microscopy. In the lower oesophageal sphincter, and at a level 2 cm above it, no apparent differences were seen in the nerve distribution pattern. Among the nerve populations studied, acetylcholinesterase (AChE)-positive nerves were the most abundant in both these regions. The density of AChE-positive nerves was particularly marked in the circular muscle layer. A rich supply of nitric oxide synthase (NOS)-containing nerves was identified by using an antiserum against neuronal NOS, or by enzyme histochemical staining for NADPH diaphorase activity. Vasoactive intestinal peptide (VIP)-immunoreactive nerves had a similar distribution pattern as NOS-immunoreactive nerves, and nerves displaying immunoreactivity for NOS and VIP often showed profiles coinciding with AChE-positive nerves. As judged by confocal microscopy, immunoreactivities for helospectin, pituitary adenylate cyclase-activating peptide (PACAP) and VIP, to a large extent were found in the same nerves. At a level 7 cm above the lower oesophageal sphincter, the total nerve supply was less than in the sphincter itself and 2 cm above it. Immunoreactivity towards VIP, PACAP and helospectin was also found to co-exist with NOS and neuropeptide Y within the same nerve structures. It is concluded that there is an intricate innervation pattern in the feline lower oesophagus reflecting the complexity in the regulation of its motility.
 ...
PMID:Nitric oxide synthase-containing, peptide-containing, and acetylcholinesterase-positive nerves in the cat lower oesophagus. 753 Nov 90

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are structurally-related neuropeptides that function as trophic factors in addition to their more classical roles as neurotransmitters. Binding and molecular cloning studies have shown that their actions are mediated by receptors encoded by at least three different genes. VIP binding has been demonstrated on many tumor types, and radiolabeled VIP has recently been used as a novel method to localize intestinal tumors in humans and their sites of metastasis. To determine the receptor subtype and level of gene expression, we screened breast, intestinal, and pancreatic, cell lines by Northern blot analysis. Breast lines expressed VIP/PACAP1 receptor mRNA levels comparable to intestinal lines, in agreement with the studies showing particularly high VIP binding in these tumors and their derived cell lines. Pancreatic cell lines expressed mRNA for several receptor types. This extends the potential utility of VIP and PACAP in the localization of tumors, and because VIP and PACAP may regulate the growth rate of some tumors by autocrine or other mechanisms, the identification of receptor subtypes on these lines sets the stage for studies in which the activity of these individual receptors in growth and other processes can be investigated.
 ...
PMID:Differential expression of VIP/PACAP receptor genes in breast, intestinal, and pancreatic cell lines. 760 May 24

Nicotinic acetylcholine (ACh) receptors (AChRs) on ciliary ganglion neurons are positively regulated by elevated cAMP levels. Vasoactive intestinal peptide (VIP) can act as a first messenger in the regulation, because application of 1 microM VIP rapidly increases both neuronal cAMP levels and ACh sensitivity. We now report that high affinity receptors for a close VIP relative, pituitary adenylate cyclase-activating polypeptide (PACAP), are present on ciliary ganglion neurons and mediate the cAMP-dependent modulation of AChRs. Consistent with the presence of PACAP type I receptors, binding studies revealed sites on the neurons having approximately 1000-fold higher affinity for the 38- and 27-amino acid forms of PACAP than for VIP, and cAMP radio-immunoassays demonstrated that PACAP38 and PACAP27 are approximately 600-fold more potent agonists for mobilizing neuronal cAMP than is VIP. In accord with their higher affinity and potency, PACAP38 and -27 (both at 10 nM) increased neuronal ACh sensitivity by approximately 50% within 10 min, whereas VIP at the same low concentration was ineffective. The increased ACh sensitivity induced by 10 nM PACAP38 or PACAP27 or 1 microM VIP depends on coincident increases in cAMP levels, because treatment of neurons with adenylate cyclase inhibitors blocked both effects. The findings demonstrate the presence of functional PACAP type I receptors on ciliary ganglion neurons that preferentially recognize PACAP38 and -27 over VIP and act via adenylate cyclase to initiate cAMP-dependent enhancement of AChR function. Finally, we detected PACAP38-like material in ciliary ganglia, suggesting a role for the peptide in modulating neuronal AChRs in vivo.
 ...
PMID:Pituitary adenylate cyclase-activating polypeptide type I receptors mediate cyclic AMP-dependent enhancement of neuronal acetylcholine sensitivity. 762 76

Vasoactive intestinal peptide (VIP) receptors were investigated in rat Harderian gland membranes using [125I]VIP as ligand. The receptor binding was rapid, reversible, saturable, specific, and dependent on time, temperature, and membrane concentration. At 30 degrees C, the stoichiometric data suggested the presence of two classes of VIP receptors with Kd values of 0.36 +/- 0.06 and 65.37 +/- 8.08 nM and binding capacities of 323 +/- 54 and 39,537 +/- 3100 fmol VIP/mg protein, respectively. The interaction showed a high degree of specificity, as suggested by competitive displacement experiments with several peptides structurally or not structurally related to VIP. The binding of [125I]VIP to membranes was sensitive to guanine nucleotides in a dose-dependent manner. The molecular characterization of VIP receptors was realized by chemical cross-linking; sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the solubilized membrane proteins revealed the presence of two specific [125I]VIP-protein complexes of M(r) 57 and 35 kDa as estimated in denaturing conditions. VIP stimulated adenylate cyclase activity in rat Harderian gland membranes in a dose-dependent manner. Finally, VIP stimulated in vivo the type II thyroxine 5'-deiodinase activity. These results demonstrate the presence of specific and functional VIP receptors in Harderian gland and suggest a role for VIP in the physiology of this gland.
 ...
PMID:VIP receptor-effector system in rat harderian gland and its coupling to activation of type II thyroxine 5'-deiodinase. 765 12

Vasoactive intestinal peptide (VIP) and peptide histidine-isoleucine (PHI) receptors and the signaling pathways to which they are coupled were characterized in dispersed gastric smooth muscle cells. Radioligand binding using 125I-labeled VIP and PHI identified 4 classes of receptors: VIP-preferring and PHI-preferring receptors recognized by both ligands and readily desensitized by the preferred ligand, and VIP-specific and PHI-specific receptors recognized by only 1 ligand and resistant to desensitization. All except VIP-specific receptors were coupled to adenylate cyclase. VIP-specific receptors mediated a G protein-coupled Ca2+ influx that led to activation of NO synthase (NOS), NO-dependent activation of soluble guanylate cyclase, and activation of guanosine 3',5'-cyclic monophosphate (cGMP) kinase resulting in muscle relaxation. The entire cascade was blocked by Ca2+ channel and/or calmodulin antagonists. The NOS inhibitor NG-nitro-L-arginine abolished L-[3H]citrulline (coproduct of NO synthesis) and cGMP generation and partly inhibited (52 +/- 4%) relaxation. The components of response mediated by VIP-specific receptors (increase in [Ca2+]i, L-[3H]citrulline, and cGMP) were preserved after desensitization. Insertion of guanosine 5'-O-(beta-thio)diphosphate into reversibly permeabilized muscle cells abolished responses mediated by VIP-preferring and VIP-specific receptors. VIP stimulated both adenosine 3',5'-cyclic monophosphate (cAMP)-kinase and cGMP-kinase activities consistent with stimulation of cAMP and cGMP. Both kinases contributed to relaxation that was partly inhibited by cAMP-kinase [H-89 and (R)-p-adenosine 3',5'-cyclic monophosphorothioate] and cGMP-kinase (KT-5823) inhibitors and abolished by a combination of the 2 types of inhibitors. We conclude that VIP-specific receptors mediate a G protein-coupled Ca2+ influx leading to activation of a constitutive Ca2+/calmodulin-dependent NOS and generation of NO, which is partly responsible for relaxation in smooth muscle.
 ...
PMID:VIP-mediated G protein-coupled Ca2+ influx activates a constitutive NOS in dispersed gastric muscle cells. 769 77

Vasoactive intestinal peptide (VIP), the structurally homologous pituitary adenylate cyclase-activating peptide (PACAP) and the pituitary hormone, prolactin (PRL) enhance rapid eye movement sleep (REMS). VIP and PACAP are both inducers of PRL gene expression and release in the pituitary gland. Little is known about PRL regulation in the brain although it is hypothesized that the REMS-promoting activity of i.c.v. administered VIP may be mediated via the activation of cerebral PRL. To test whether VIP or PACAP in fact increase intracerebral mRNA, the peptides (VIP: 30 or 300 pmol; PACAP: 220 pmol) were injected i.c.v. into rats at dark onset. 1 h later, cDNA was synthesized from purified hypothalamic mRNA. Standardized amounts were analysed for PRL using the polymerase chain reaction followed by Southern blotting and hybridization. Compared with beta-actin mRNA levels, both VIP and PACAP increased PRL mRNA levels in a dose-dependent fashion though VIP was more effective on a molar basis. The previously reported alternatively spliced PRL mRNA (lacking exon 4) was not detected. The data support the hypothesis that the REMS-promoting activity of central VIP and PACAP might be mediated by cerebral PRL.
 ...
PMID:Increase of prolactin mRNA in the rat hypothalamus after intracerebroventricular injection of VIP or PACAP. 782 Jun 99

Vasoactive intestinal peptide (VIP) is widely recognized as a regulator of tyrosine hydroxylase via a mechanism of trans-synaptic activation. Subsets of adrenal medullary cells and postganglionic sympathetic nerves coexpress the peptide neurotransmitter neuropeptide Y (NPY) with catecholamines. Using PC12 cells transiently expressing a fusion gene in which the bacterial enzyme chloramphenicol acetyltransferase (CAT) is under the control of 700 base pairs of the 5' flanking region of the NPY gene, we have studied the role of VIP and the related peptide pituitary adenylate cyclase activating peptide (PACAP) in regulating NPY gene transcription. Both VIP and PACAP stimulated expression of the NPY gene through activation of cAMP-dependent protein kinase. PACAP was 1000-fold more potent in eliciting this response compared to VIP and activity resided in its N-terminal 27 amino acids. Both VIP and PACAP caused a subpopulation (approximately 50%) of PC12 cells to undergo profound morphological changes in that the cells extended long, slender neurites with prominent growth cones. This change in morphology was unaffected by preincubating cells with inhibitors of either cAMP-dependent protein kinase or calcium/phospholipid-dependent protein kinase. A trophic role for either VIP or PACAP in regulating sympathetic nerve function is proposed.
 ...
PMID:Vasoactive intestinal peptide stimulates neuropeptide Y gene expression and causes neurite extension in PC12 cells through independent mechanisms. 796 4


<< Previous 1 2 3 4 5 6 7 8 9 Next >>