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

---

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

In accord with previous studies, it was found that vasoactive intestinal peptide (VIP), a powerful activator of adenylate cyclase, and cAMP-active agents (i.e., 8-Br-cAMP, forskolin, and Ro20-1724) increased the firing rate of noradrenergic neurons in the locus coeruleus (LC) by inducing an inward current. The response to VIP was usually more rapid and larger in a subpopulation of LC neurons with subthreshold rhythmic oscillations in membrane potential (oscillatory cells) as compared to nonoscillatory cells. In either case, the inward currents elicited by VIP and cAMP-active agents were found to be nonadditive, suggesting the action of VIP, at least in part, is via the same mechanism as that of cAMP-active agents. Intracellular application of a specific protein (or related peptide) inhibitor of cAMP-dependent protein kinase markedly attenuated the activation induced by either cAMP-active agents or VIP, suggesting that cAMP-dependent protein kinase (protein kinase A), presumably through protein phosphorylation, plays a role in the action of VIP. Taken together, the results provide evidence that cAMP and protein kinase A are involved in mediating the electrophysiological actions of VIP on LC neurons.
...
PMID:Excitation of locus coeruleus neurons by vasoactive intestinal peptide: role of a cAMP and protein kinase A. 217 May 95

GRF promotes follicular maturation and ovulation when administered with FSH in the treatment of infertility. Such actions could be mediated by stimulation of GH secretion and insulin-like growth factor I production, but the known actions of the structurally related hormone, vasoactive intestinal peptide (VIP), on granulosa cell function suggested that GRF may also act directly on the ovary to stimulate follicular development. Radioligand binding and activation studies, performed in granulosa cells from immature estrogen-treated rats, revealed a common receptor for VIP and rat (r) GRF in the ovary. Specific binding of [125I]VIP to granulosa cells was saturable and dependent on time and temperature. The relative potencies of VIP-related peptides for inhibition of radioligand binding were: VIP greater than rGRF greater than peptide histidine isoleucinamide greater than [His1,Nle27] human GRF(1-32)NH2 greater than secretin. In binding studies with the potent GRF agonist, [125I] [His1,Nle27]GRF(1-32)NH2, relative potencies were: rGRF(1-43)OH greater than [His1,Nle27]human GRF(1-32)NH2 greater than VIP greater than peptide histidine isoleucinamide greater than secretin. Glucagon and gastric inhibitory peptide, other peptides of the glucagon superfamily, and unrelated peptides including CRF and beta-endorphin, did not inhibit binding of either radioligand to ovarian receptors. In cultured granulosa cells, rGRF and VIP stimulated cAMP formation, consistent with coupling of their receptors to the adenylate cyclase system, and potentiated FSH-induced cAMP production. Both peptides also amplified FSH-induced progesterone biosynthesis, aromatase activity, and LH receptor formation. These observations demonstrate that rGRF is a potent cAMP-mediated agonist in the rat ovary and acts on a common VIP/GRF receptor in maturing granulosa cells. It is likely that the potentiating effect of administered GRF on gonadotropin-stimulated follicular development in vivo is in part mediated by direct actions of the peptide on the VIP/GRF receptor. Also, since GRF is present in the gonads, it is possible that the locally-produced peptide promotes follicular maturation by paracrine modulation of the stimulatory action of FSH on granulosa cell function.
...
PMID:Receptor-mediated actions of growth hormone releasing factor on granulosa cell differentiation. 217 7

Striatal neurons in primary culture express a wide variety of adenylate cyclase-coupled receptors, and particularly dopamine (DA) D1 receptors, which are known to induce an increase in cyclic AMP production. To study desensitization of those receptor-mediated responses, neurons were incubated in the presence of saturating concentrations of DA for various times. We observed a rapid desensitization of the D1 response after 15 min, which reached a maximum after 18 h. This effect is reversible since incubation of treated neurons in fresh medium led to a complete recovery of the dopamine response within 2 days. In addition, a brief treatment with DA resulted in heterologous desensitization of beta-adrenoceptors and 5-HT and vasoactive intestinal peptide (VIP) receptors coupled to adenylate cyclase on striatal neurons. Similar to what was observed for homologous desensitization, these effects are obtained within the first 15 min of exposure to DA; however, they are short-lasting, even in the persistent presence of DA.
...
PMID:Dopamine-induced homologous and heterologous desensitizations of adenylate cyclase-coupled receptors on striatal neurons. 217

Regulation of active K+ influx and Na(+)-K(+)-Cl- cotransport activity in HT-29 cells by vasoactive intestinal peptide (VIP) was investigated. Both active K+ influx, defined as the ouabain-sensitive component, and Na(+)-K(+)-Cl- cotransport, defined as the ouabain-resistant bumetanide-sensitive component, of total K+ uptake were increased by VIP. VIP increased the maximum velocity (Vmax) values for both components with no change in apparent Michaelis constant (Km) values. Three lines of evidence support the role of adenosine 3',5'-cyclic monophosphate (cAMP) as a mediator of the VIP effects. 1) The rank order potencies of VIP and peptide histidineisoleucineamide (PHI) in binding and cAMP production (J. T. Turner, S. B. Jones, and D. B. Bylund, Peptides Fayetteville 7: 849, 1986) and K+ uptake were consistent; 2) alpha 2-adrenergic agonists inhibited both VIP-stimulated cAMP production (J. T. Turner, C. Ray-Prenger, and D. B. Bylund, Mol. Pharmacol. 28: 422, 1985) and K+ uptake; and 3) forskolin, but not dideoxyforskolin, mimicked the effects of VIP on K+ uptake. Because amiloride blocked the VIP-stimulated active K+ component, the VIP effects on active K+ influx may be secondary to a Na(+)-H+ antiporter-mediated increase in cellular Na+ content. Additional experiments indicated that pretreatment of cells with a protein kinase C activator, previously shown to decrease basal Na(+)-K(+)-Cl- cotransport activity and the apparent number of cotransporters in HT-29 cells (C. C. Franklin, J. T. Turner, and H. D. Kim, J. Biol. Chem. 264: 6667, 1989), did not change the magnitude of response of the remaining cotransporters after adenylate cyclase activation.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Vasoactive intestinal peptide stimulates active K+ transport and Na(+)-K(+)-Cl- cotransport in HT-29 cells. 230 69

Vasoactive intestinal polypeptide (VIP) was incubated in an adenylate cyclase assay with a particulate fraction of caudate-putamen (CP) tissue of the rat in order to examine the effect of the peptide on forskolin-activated adenylate cyclase in vitro. Forskolin induced an enhancement of cyclic AMP formation that was mediated by an effect on catalytic subunit and stimulatory guanine nucleotide regulatory protein (Ns). In our preparation, VIP did not influence basal adenylate cyclase activity or the stimulation by dopamine and sodium fluoride but, in the absence of guanylylimidodiphosphate (guanosine 5'-(beta, y-imido)-triphosphate) VIP inhibited the forskolin-stimulation of the enzyme in a noncompetitive manner. Met-encephalin, acting on a D-2 receptor-coupled putative inhibitory guanine nucleotide regulatory protein (Ni), inhibited the adenylate cyclase activity stimulated by forskolin to a slightly greater extent than VIP. When assayed together, these inhibition effects were additive, implying that the peptide receptors are not identical. The Ni-antagonist, MnCl2 completely blocked the inhibition of met-encephalin but had no significant effect on VIP-induced inhibition. In addition, pertussis toxin did not influence the effect of VIP on forskolin-stimulation in contrast to cholera toxin which did antagonize the VIP effect via the stimulatory guanine nucleotide regulatory protein (Ns). Furthermore, specific D-1 and D-2 dopaminergic receptor antagonists alpha(+)-flupentixol and spiperone had no effect on VIP-modulated forskolin-stimulated adenylate cyclase activity. These results suggest that the neuromodulatory effect of VIP is mediated by a Ns distinct from those involved in several adenylate cyclase pools sensitive to stimulation by dopamine and VIP in the rat striatum.
...
PMID:The effect of vasoactive intestinal polypeptide (VIP) on forskolin stimulated adenylate cyclase in the caudate-putamen of the rat. 232 84

A novel bioactive peptide was recently isolated from ovine hypothalamus and was named PACAP (pituitary adenylate cyclase-activating polypeptide). PACAP was present in two bioactive, amidated forms, PACAP27 and PACAP38 (27 and 38 amino acids, respectively), and showed a 68% sequence homology with vasoactive intestinal peptide (VIP) in the N-terminal 28 residues. PACAP38 was at least 1000 times more potent than VIP in stimulating adenylate cyclase in pituitary cells, but both peptides exhibited comparable vasodepressor activity. Thus, we sought to determine whether PACAP acts on specific binding sites in the anterior pituitary or other tissues and whether these binding sites are different from those of VIP. Binding of [125I] PACAP27 to freshly prepared rat anterior pituitary membranes in the presence and absence of 212 nM unlabeled PACAP27 was specific, saturable, and more rapid at 22 C than at 4 C. Scatchard analysis of this binding site using increasing doses of unlabeled PACAP27 revealed a single high affinity site with a Kd of 446 +/- 141 pM and a maximum number of sites of 1312 +/- 182 fmol/mg protein. These results do not exclude the possibility of a second pituitary binding site with significantly lower affinity. Unlabeled PACAP38 and PACAP38OH exhibited significantly higher affinity binding (3- to 5-fold) than PACAP27 with a similar number of pituitary sites. A variable distribution of binding sites was observed between PACAP27 and VIP when binding to different tissue membranes was measured with 125I-labeled peptides. Very high specific binding of both PACAP27 and VIP was observed in lung membranes. An almost identical relative magnitude of binding was observed between PACAP27 and VIP in lung, liver, duodenum, ovary, and thymus. However, whereas PACAP27 binding to hypothalamic and pituitary membranes was great, VIP binding to these tissues was almost absent. To determine if VIP and PACAP might share a binding site in peripheral tissues, displacement curves were generated using [125I]PACAP27 binding to lung membranes and VIP, PACAP27, and PACAP38 as unlabeled ligands. VIP was highly potent in displacing [125I] PACAP27 binding in lung membrane, and the IC50 values for all three of these peptides were between 1-10 nM. These results suggest that 1) a saturable, high affinity binding site for PACAP is present on anterior pituitary membranes; 2) PACAP27 and PACAP38, but not VIP, share this binding site in the anterior pituitary and possibly the hypothalamus; and 3) PACAP27, PACAP38, and VIP share a similar or identical binding site on lung membranes and possibly other peripheral tissues.
...
PMID:Characterization and distribution of binding sites for the hypothalamic peptide, pituitary adenylate cyclase-activating polypeptide. 236 73

The effect of adenosine and its analogue (-)-N6-R-phenylisopropyladenosine (PIA) on both anterior pituitary adenylate cyclase activity and prolactin secretion was examined in the rat. Adenosine inhibited basal adenylate cyclase activity in a dose-dependent manner and also reduced the stimulation of the enzyme by vasoactive intestinal peptide (VIP). Likewise, in primary cultures of anterior pituitary cells, adenosine decreased prolactin secretion in both basal and VIP-stimulated conditions. In perifusion experiments, adenosine also inhibited prolactin release in both basal and TRH-stimulated conditions. PIA produced a biphasic pattern of response of basal adenylate cyclase activity, being inhibitory at low and stimulatory at high concentrations. In VIP-stimulated conditions, low concentrations of PIA inhibited both adenylate cyclase activity and prolactin release from primary cultures of pituitary cells, while no additive stimulatory effect was seen at high concentrations. Similarly, low concentrations of PIA reduced both basal and TRH-stimulated prolactin release from perifused pituitaries, while increasing PIA concentrations restored prolactin release. These data show that adenosine affects basal and stimulated prolactin secretion from anterior pituitary cells. Adenosine receptors seem to be coupled to the adenylate cyclase system in the anterior pituitary gland, suggesting a possible relationship between the effect of adenosine on adenylate cyclase activity and prolactin secretion.
...
PMID:Adenosine and its analogue (-)-N6-R-phenyl-isopropyladenosine modulate anterior pituitary adenylate cyclase activity and prolactin secretion in the rat. 239 24

Recent findings indicate that interleukin-1 beta (IL1 beta), a monokine secreted by stimulated macrophages and monocytes, modulates neuroendocrine functions in a manner similar to classical hormones. In this study we show that IL1 modulates PRL secretion, assessed by reverse hemolytic plaque assay, and describe the effect of the monokine on adenylate cyclase activity and calcium fluxes in rat normal pituitary cells. In basal and vasoactive intestinal peptide (VIP)-stimulated conditions, low doses of IL1 reduced the mean plaque area, a direct index of PRL secretion without affecting the percentage of PRL-secreting cells. Similarly, low concentrations of IL1 inhibited adenylate cyclase activity in both basal and VIP-stimulated conditions, while higher concentrations restored the enzymatic activity to the control value. IL1 also caused a biphasic effect on the free intracellular calcium increase induced by maitotoxin, a calcium channel activator, being inhibitory at low and stimulatory at high concentrations. The effects of IL1 on adenylate cyclase activity and calcium fluxes were reversed by preincubation of the monokine with its polyclonal antibody, thus confirming the specificity of the effects. In conclusion, our data show that IL1 modulates PRL secretion by acting directly on pituitary cells through interaction with the adenylate cyclase-cAMP system and calcium flux.
...
PMID:Interleukin-1-beta modulation of prolactin secretion from rat anterior pituitary cells: involvement of adenylate cyclase activity and calcium mobilization. 240 18

Although 3,4-dihydroxyphenylethylamine (dopamine, DA) and vasoactive intestinal peptide (VIP) have been reported to stimulate adenylate cyclase activity in the rabbit retina, possible interactions between VIP-sensitive and DA-sensitive adenylate cyclase systems have not been previously investigated. To elucidate the interactions between these two putative transmitter-stimulated cyclase systems, the effects of VIP, DA, and VIP + DA on the conversion of [alpha-32P]ATP to [32P]cyclic AMP in rabbit retinal homogenates were measured. VIP stimulated adenylate cyclase activity in a biphasic manner, suggesting that two classes of VIP receptors may be involved in the induction of cyclic AMP formation. DA was less potent than VIP, and stimulated cyclase activity with a monophasic dose-response curve. When assayed together, these stimulations were partially nonadditive, implying the existence of a common adenylate cyclase pool that may be stimulated by both putative neurotransmitters. The dopaminergic antagonist (+)-butaclamol completely blocked dopaminergic stimulation, but had no significant effect on VIP-induced stimulation, indicating that VIP interacts with specific VIP receptor sites, which are distinct from the dopaminergic receptor sites. Furthermore, the specific D-2 dopaminergic receptor agonist LY141865 demonstrated no inhibitory effect on adenylate cyclase activity, suggesting that the interaction between the VIP- and DA-sensitive adenylate cyclase systems does not result from a D-2 receptor-mediated cyclase inhibition in the rabbit retina. Finally, at maximally effective concentrations, DA and VIP were less potent than fluoride or forskolin in the stimulation of cyclic AMP formation, suggesting that adenylate cyclase pools that are not sensitive to DA and VIP may also be present in this retina.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Interactions between vasoactive intestinal peptide and dopamine in the rabbit retina: stimulation of a common adenylate cyclase. 241 80

Previous studies have shown that left ventricular (LV) hypertrophy in renal hypertensive rats (RHR) is associated with reduced responsiveness to beta-adrenergic stimulation (isoproterenol) but not to calcium or cardiac glycosides. To determine whether this impairment is restricted to beta-receptor agonists or extended to include other stimulants of the adenylate cyclase system, inotropic responses to glucagon and to vasoactive intestinal peptide (VIP) were determined in isolated paced hearts (Langendorff preparation) from RHR and strictly matched sham-operated controls. The response (delta peak LV +dP/dt) to both agonists was significantly reduced in RHR, whether expressed in absolute value or in percent of baseline. It averaged 59.3 +/- 19.3 (SE) mm Hg X s-1 in RHR at the highest dose of VIP (15 micrograms) and a perfusion pressure (PP) of 50 mm Hg as compared with 255 +/- 68.4 in controls (p less than 0.01). The responses to glucagon were determined at two levels of perfusion pressure--50 and 80 mm Hg--to determine the influence, if any, of possible alterations in myocardial perfusion on differences between the normal and hypertrophied hearts. At both PP levels the LV +dP/dt response was significantly lower in RHR--+ 374 +/- 103 vs. + 1,026 +/- 166 mm Hg X s-1 (p less than 0.005) or + 120 +/- 5 vs. + 143 +/- 7% of baseline value (p less than 0.02) for PP of 50 mm Hg; and 392 +/- 154 vs. + 1,732 +/- 251 mm Hg X s-1 (p less than 0.01) or + 112 +/- 4 vs. + 160 +/- 2% (p less than 0.001) for PP of 80 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Inotropic responsiveness in hypertensive left ventricular hypertrophy: impaired inotropic response to glucagon and vasoactive intestinal peptide in renal hypertensive rats. 242 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---