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)

1. The involvement of second messengers and of other chemical mediators, in the modulation of the membrane potential of the Schwann cell of the giant nerve fiber of the Tropical squid Sepioteuthis sepioidea is described. 2. The involvement of the cyclic nucleotide adenosine 3', 5' monophosphate (cAMP) in mediating the actions of the nicotinic Ach receptors of the Schwann cells is suggested. 3. The presence of octopaminergic receptors in the Schwann cells, mediating their actions through the activation of adenylate cyclase, is also described. 3. Receptors for vasoactive intestinal peptide (VIP) are also present on the Schwann cells, and their actions are mediated via a second messenger system that does not involve the activation of adenylate cyclase. 5. The three independent receptor systems referred above are able to interact in a complex way, which involves both their direct actions on the Schwann cell membrane potential and modulatory effects between the systems.
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PMID:Modulation of the membrane potential of the Schwann cell of the squid giant nerve fiber. 284 30

We examined the mechanism by which adenosine inhibits prolactin secretion from GH3 cells, a rat pituitary tumour line. Prolactin release is enhanced by vasoactive intestinal peptide (VIP), which increases cyclic AMP, and by thyrotropin-releasing hormone (TRH), which increases inositol phosphates (IPx). Analogues of adenosine decreased prolactin release, VIP-stimulated cyclic AMP accumulation and TRH-stimulated inositol phospholipid hydrolysis and IPx generation. Inhibition of InsP3 production by R-N6-phenylisopropyladenosine (R-PIA) was rapid (15 s) and was not affected by the addition of forskolin or the removal of external Ca2+. Addition of adenosine deaminase or the potent adenosine-receptor antagonist, BW-A1433U, enhanced the accumulation of cyclic AMP by VIP, indicating that endogenously produced adenosine tonically inhibits adenylate cyclase. The potency order of adenosine analogues for inhibition of cyclic AMP and IPx responses (measured in the presence of adenosine deaminase) was N6-cyclopentyladenosine greater than R-PIA greater than 5'-N-ethylcarboxamidoadenosine. This rank order indicates that inhibitions of both cyclic AMP and InsP3 production are mediated by adenosine A1 receptors. Responses to R-PIA were blocked by BW-A1433U (1 microM) or by pretreatment of cells with pertussis toxin. A greater amount of toxin was required to eliminate the effect of R-PIA on inositol phosphate than on cyclic AMP accumulation. These data indicate that adenosine, in addition to inhibiting cyclic AMP accumulation, decreases IPx production in GH3 cells, possibly by directly inhibiting phosphoinositide hydrolysis.
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PMID:Regulation of GH3-cell function via adenosine A1 receptors. Inhibition of prolactin release, cyclic AMP production and inositol phosphate generation. 284 12

Among several effects, ethanol (EtOH) interferes with membrane fluidity and lipid-protein interactions. As proteins are influenced by surrounding lipids, the activity of membrane-bound enzymes such as adenylate cyclase (AC) could be modulated by EtOH, as shown in potentiating, at toxic concentrations, the stimulating effect of hormones or neurotransmitters. We have also found that EtOH potentiates in a dose-dependent manner (EC50 = 100 mM) the cAMP production elicited by vasoactive intestinal peptide (VIP), already noticeably at 70 mM, without affecting basal cAMP levels (up to 400 mM). Propanol produces a similar potentiation, whereas methanol was inactive. Butanol (200 mM) displays toxic effects. The potentiation induced by EtOH is similar for peptide- (VIP) or monoamine- (noradrenaline) stimulated cAMP formation, suggesting a primary action at a interaction between VIP and NA in stimulating cAMP formation.
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PMID:Effects of ethanol on VIP-and/or noradrenaline-stimulated cAMP formation in mouse brain. 285 74

Adenylate cyclase stimulation by GH-releasing factor (GRF) and 14 GRF analogs (modified in the N-terminal part) was compared to the capacity of the same peptides to inhibit [125I]iodo-vasoactive intestinal peptide (VIP) binding in rat pancreatic plasma membranes. These peptides interfered with VIP receptors as they inhibited [125I]iodo-VIP binding, and probably acted through VIP-preferring receptors as one of these peptides [(N-Ac-Tyr1,D-Phe2)-GRF(1-29)-NH2] selectively inhibited both VIP- and GRF-stimulated adenylate cyclase activities. In general, alterations in positions 6 and 7 (but not in positions 1-4) markedly reduced the affinity of the resulting GRF analog [based on Kact (concentration exerting half-maximal stimulation) values]. The intrinsic activity exerted by GRF analogs on adenylate cyclase was reduced by acetylation of the free NH2 group and by the replacement of Asp3, Ala4, Phe6, and Thr7 by the corresponding D-isomer. The presence of pCl-Phe6 and Trp6 also depressed this parameter. Substitution in GRF (or its N-acetylated derivative) by D-Phe2, D-Arg2, and D-Ala4 again reduced the intrinsic activity, whereas substitution of the natural L-amino acid residue by D-Ala2 and Phe4 gave superagonists.
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PMID:Interaction of growth hormone-releasing factor (GRF) and 14 GRF analogs with vasoactive intestinal peptide (VIP) receptors of rat pancreas. Discovery of (N-Ac-Tyr1,D-Phe2)-GRF(1-29)-NH2 as a VIP antagonist. 285 87

Evidence is rapidly accumulating to support the existence of a neuroimmune axis. However, the precise role of individual neurotransmitters in regulating immune function remains to be elucidated. In this review we focus on the role of vasoactive intestinal peptide (VIP) in modulation of lymphocyte function. We examine its status as a neurotransmitter, including evidence for neuronal and possible extraneuronal sites of synthesis. Further, we present data to demonstrate the presence of VIP receptors in human lymphocytes and, using the Molt 4b lymphoblastic cell line as a model, show VIP-mediated activation of adenylate cyclase leading to cAMP-dependent protein kinase-mediated phosphorylation of a specific Molt protein. Finally, we discuss the functional significance of VIP receptors on lymphocytes and present a model of neuropeptide-induced inflammation with possible therapeutic applications of this exciting new field of neuroimmunology.
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PMID:Vasoactive intestinal peptide and neuropeptide modulation of the immune response. 286 Dec 33

The rectal gland of the spiny dogfish Squalus acanthias is stimulated to secrete chloride by vasoactive intestinal peptide (VIP) in a way that is inhibited by somatostatin. The mechanism of inhibition by somatostatin was studied in isolated perfused rectal glands and separated rectal gland cells. Somatostatin did not alter the specific binding of VIP to rectal gland cells but inhibited their accumulation of adenosine 3',5'-cyclic monophosphate (cAMP) in response to VIP. In isolated perfused glands, somatostatin inhibited the stimulation of secretion produced by VIP, adenosine, and forskolin, as well as by dibutyryl cAMP plus a phosphodiesterase inhibitor. The results support the hypothesis of both a proximal and a distal locus, in the cascade of events leading from adenylate cyclase activation to cellular response, at which somatostatin exerts an inhibitory effect.
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PMID:Mode of action of somatostatin to inhibit secretion by shark rectal gland. 286 85

The neuropeptide somatostatin inhibits hormone release from GH4C1 pituitary cells via two mechanisms: inhibition of stimulated adenylate cyclase and a cAMP-independent process. To determine whether both mechanisms involve the guanyl nucleotide-binding protein Ni, we used pertussis toxin, which ADP-ribosylates Ni and thereby blocks its function. Pertussis toxin treatment of GH4C1 cells blocked somatostatin inhibition of both vasoactive intestinal peptide (VIP)-stimulated cAMP accumulation and prolactin secretion. In membranes prepared from toxin-treated cells, somatostatin inhibition of VIP-stimulated adenylate cyclase activity was reduced and 125I-Tyr1-somatostatin binding was decreased more than 95%. In contrast, pertussis toxin did not affect the biological actions or the membrane binding of thyrotropin-releasing hormone. These results indicate that ADP-ribosylated Ni cannot interact with occupied somatostatin receptors and that somatostatin inhibits VIP-stimulated adenylate cyclase via Ni. To investigate somatostatin's cAMP-independent mechanism, we used depolarizing concentrations of K+ to stimulate prolactin release without altering intracellular cAMP levels. Measurement of Quin-2 fluorescence showed that 11 mM K+ increased intracellular [Ca2+] within 5 s. Somatostatin caused an immediate, but transient, decrease in both basal and K+-elevated [Ca2+]. Consistent with these findings, somatostatin inhibited K+-stimulated prolactin release, also without affecting intracellular cAMP concentrations. Pertussis toxin blocked the somatostatin-induced reduction of [Ca2+]. Furthermore, the toxin antagonized somatostatin inhibition of K+-stimulated and VIP-stimulated secretion with the same potency (ED50 = 0.3 ng/ml). These results indicate that pertussis toxin acts at a common site to prevent somatostatin inhibition of both Ca2+- and cAMP-stimulated hormone release. Thus, Ni appears to be required for somatostatin to decrease both cAMP production and [Ca2+] and to inhibit the actions of secretagogues using either of these intracellular messengers.
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PMID:Pertussis toxin blocks both cyclic AMP-mediated and cyclic AMP-independent actions of somatostatin. Evidence for coupling of Ni to decreases in intracellular free calcium. 286 57

When individually tested, vasoactive intestinal peptide (VIP), cholera toxin, and monoclonal thyroid-stimulating antibodies (TSAbs), but not TSH binding-inhibiting antibodies (TBIAbs), elevate cAMP levels in cultured human thyroid cells. In this study, we tested the effect on cAMP levels in human thyroid cells of the simultaneous presence of VIP and the other ligands noted. Monoclonal TBIAbs (11E8 and 122G3), which interact with a membrane glycoprotein containing the high affinity binding site of the TSH receptor, did not alter VIP-induced cAMP accumulation in the thyroid cells. These data indicate that VIP and TSH bind to distinct sites on the cell membrane. In contrast, monoclonal TSAbs 208F7 and 307H6, which interact with a portion of the TSH receptor other than its high affinity binding site, not only did not have their usual agonist activity, but, instead, caused a marked inhibition of human thyroid cAMP accumulation when VIP was also present. Mutual antagonism by two agonists, i.e. inhibition evident when TSAbs and VIP were mixed, was also found when cholera toxin was coincubated with VIP. The inhibitory effect of mixing cholera toxin and VIP was nearly immediate and was duplicated with mixtures of the beta-subunit of cholera toxin and VIP. The inhibition evident in mixing VIP and the TSAbs or cholera toxin was not duplicated in mixtures of isoproterenol and VIP or in mixtures of forskolin and VIP. These results suggest that the mutual inhibition of VIP and either TSAbs or cholera toxin is at a step that couples the TSH and VIP high affinity receptor-binding sites to the adenylate cyclase complex.
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PMID:Unusual antagonistic actions of mixtures of vasoactive intestinal peptide, thyroid-stimulating antibodies, and cholera toxin on adenosine 3',5'-monophosphate accumulation in normal human thyroid cell cultures. 287 Oct 39

We have investigated the influences of gonadal and adrenal hormones on neurotransmitter-stimulated cyclic adenosine 3',5'-phosphate (cAMP) formation in hippocampal slices from male and female rats. We found that castration of male rats specifically decreases histamine-stimulated cAMP accumulation, as does administration of estradiol plus progesterone to ovariectomized female rats. In ovariectomized females, activation of cAMP accumulation by isoproterenol was also reduced by estradiol plus progesterone treatment. Although neither of these endocrine manipulations significantly affected stimulation of cAMP accumulation by vasoactive intestinal peptide (VIP), regulation of VIP-stimulated cAMP generation by glucocorticoids was found in female rats. However, the direction of the effect of the synthetic glucocorticoid dexamethasone in females was opposite to its previously demonstrated action in males. These results suggest that gonadal and other steroids may specifically modulate the responsiveness of components of the adenylate cyclase system to certain neurotransmitters, and that such regulation may differ between the sexes and may occur in telencephalic brain regions such as the hippocampus.
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PMID:Gonadal steroid modulation of neurotransmitter-stimulated cAMP accumulation in the hippocampus of the rat. 288 11

The mechanism by which somatostatin acts to modulate cholinergic transmission is not clear. In this study we investigated the role of the adenosine 3',5'-cyclic monophosphate (cAMP) system in mediating cholinergic transmission in the guinea pig myenteric plexus and examined the ability of somatostatin to alter acetylcholine (ACh) release stimulated by various cAMP agonists. Forskolin, 8-bromo-cAMP, vasoactive intestinal peptide (VIP), and cholera toxin each stimulated the release of [3H]ACh in a dose-related manner. Addition of theophylline enhanced the release of [3H]ACh stimulated by these cAMP agonists. In contrast 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, antagonized the action of forskolin, VIP, and cholera toxin but had no effect on that evoked by 8-bromo-cAMP. These observations suggest that cAMP may serve as a physiological mediator for ACh release from myenteric neurons. Somatostatin inhibited release of [3H]ACh evoked by various cAMP agonists in a dose-related manner. Maximal inhibition, observed in the presence of 10(-6) M somatostatin was 48 +/- 5, 47 +/- 9, and 43 +/- 12% of control for forskolin-, VIP-, and cholera toxin-evoked release of [3H]ACh. In contrast somatostatin at 10(-6) M inhibited only 20 +/- 5% of the release of [3H]ACh stimulated by 8-bromo-cAMP. Pretreatment with pertussis toxin antagonized the inhibitory effect of somatostatin on the release of [3H]ACh evoked by forskolin, VIP, or cholera toxin but had no effect on the inhibitory action of somatostatin on the release of [3H]ACh evoked by 8-bromo-cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Somatostatin inhibits cAMP-mediated cholinergic transmission in the myenteric plexus. 289 4


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