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)

Receptor-effector coupling in the adenylate cyclase (AC) system was studied using fusion transfer of rat or monkey frontal cortex membranes to Friend erythroleukemia (Fc) cells. The indigenous AC activity of cortex membranes had previously been inactivated with N-ethylmaleimide. In the fusates, the AC activity could be stimulated through beta-adrenoceptors using noradrenaline (NA), or through specific receptors for vasoactive intestinal polypeptide (VIP), or by fluoride which activates the effector components of the AC-system directly, bypassing receptors. There was a critical stoichiometric relationship between the receptor-stimulated cAMP output and the number of recipient cells of the fusion system, i.e. the total AC capacity as measured by fluoride stimulation. In fusates with rat brain membranes, the beta-adrenoceptor coupling increased as the availability of recipient cells increased; on the other hand, the excess of recipient cells did not change the VIP receptor coupling capacity. In fusates with monkey brain membranes, the situation was the opposite: VIP receptor coupling increased as larger amounts of recipient cells were made available, but the beta-adrenoceptor coupling capacity remained unchanged. The differences in coupling capacities were related to differences in receptor binding with higher beta-adrenoceptor density in rat than in monkey frontal cortex membranes, as opposed to higher VIP receptor density in monkey than in rat frontal cortex membranes. Neuropeptide tyrosine (NPY) attenuated both NA- and VIP-induced activation of AC in the fusates; it was equally potent against both agents. In rat brain membrane fusates, the NA-induced AC activity was attenuated in a dose-dependent and apparently non-competitive manner.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Coupling of receptors in brain membranes by fusion to the adenylate cyclase system of a foreign effector cell. 285 88

Neuropeptide Y, a major neuropeptide and potent vasoconstrictor, inhibited isoproterenol-stimulated adenylate cyclase activity in cultured rat atrial cells as well as in atrial membranes. Prior treatment of the cells with pertussis toxin blocked the inhibitory action of neuropeptide Y. Pertussis toxin is known to uncouple the receptors for other inhibitors of adenylate cyclase by ADP-ribosylation of the alpha-subunit of Gi, the inhibitory guanine nucleotide binding component of adenylate cyclase. The toxin specifically catalyzed the ADP-ribosylation of a 41-kilodalton atrial membrane protein which corresponded to the Gi subunit. These results suggest that neuropeptide Y may mediate some of its physiological effects through specific receptors linked to the inhibitory pathway of adenylate cyclase.
...
PMID:Neuropeptide Y inhibits cardiac adenylate cyclase through a pertussis toxin-sensitive G protein. 302 13

The effects of neuropeptide Y (NPY) on cyclic AMP (cAMP) accumulation in slices of the dorsal midline area of the caudal part of the medulla oblongata containing the nucleus tractus solitarius (nTS) have been studied. Neuropeptide Y (30 and 300 nM) significantly reduced the [3H]cAMP accumulation induced by forskolin and phorboldibutyrate. Similar results were obtained after incubation with the alpha-adrenoceptor agonist clonidine (1 microM). These results indicate that stimulation of the NPY receptors and alpha-adrenoceptors in the nTS region may cause inhibition of the adenylate cyclase. Such a mechanism may at least partly underlie the centrally mediated hypotensive effects of the costored transmitters adrenaline and NPY.
...
PMID:Inhibitory effects of neuropeptide Y on cyclic AMP accumulation in slices of the nucleus tractus solitarius region of the rat. 303 37

Neuropeptide Y (NPY), a peptide often coreleased with catecholamines, appears to be an important component of the sympathetic nervous system, but little is known about the molecular basis of its action. We introduce here human erythroleukemia (HEL) cells as a new model system for studies of NPY action. NPY inhibited adenosine 3,5'-cyclic monophosphate (cAMP) accumulation in HEL cells with a 50% effective concentration (EC50) of 3 nM. Additionally NPY increased intracellular Ca2+, as assessed by fura-2 fluorescence, with a similar EC50. Pretreatment with pertussis toxin blocked both responses, suggesting the involvement of one or more G proteins. Chelating extracellular Ca2+ with EGTA did not reduce the Ca2+ signal, demonstrating mobilization from intracellular stores rather than influx. Experiments with various agents demonstrated that the Ca2+ mobilization was not secondary to lowering of cAMP levels, formation of arachidonic acid products, or Na+-H+ exchange. Ca2+ mobilization also did not appear to be associated with inositol phosphate generation. In conclusion, we demonstrate for the first time that NPY, in addition to inhibiting adenylate cyclase, also can elevate intracellular Ca2+. HEL cells should prove useful in further studies of the molecular basis of NPY action.
...
PMID:Neuropeptide Y mobilizes Ca2+ and inhibits adenylate cyclase in human erythroleukemia cells. 320 64

Neuropeptide Y inhibited the forskolin-stimulated adenylate cyclase activity in rat hippocampus with the half-maximal effect occurring at 73 nM. The maximal inhibition corresponded to a 17-22% decrease of the control level of enzyme activity. The effect of neuropeptide Y was mimicked by the peptide YY but not by the avian pancreatic polypeptide and required micromolar concentrations of GTP. These results indicate that, in the brain, the inhibition of adenylate cyclase activity constitutes a mechanism by which the receptor for neuropeptide Y transduces its signal.
...
PMID:Neuropeptide Y inhibits forskolin-stimulated adenylate cyclase activity in rat hippocampus. 360 27

Neuropeptide Y (NPY) is a 36 amino acid peptide present in the central and peripheral nervous systems. Treatment with Nerve Growth Factor (NGF) induces an increase in NPY mRNA in PC12 cells, a rat pheochromocytoma cell line extensively used as a model of neuronal differentiation. Stimulators of both cAMP and calcium-phospholipid dependent protein kinases (PKA and PKC respectively) increase NPY mRNA levels in a similar way to NGF. Nevertheless, H-89, a specific inhibitor of PKA failed to block NGF stimulated NPY mRNA accumulation. Furthermore, direct measurement of PKA activity in cell extracts showed no increase following NGF, in contrast to forskolin. H7, an inhibitor of both PKC and PKA systems completely abolished the NGF induced increase in NPY mRNA, suggesting that PKC is necessary for NGF induction of the NPY gene. NGF also increased PKC activity in cell extracts in a similar way to phorbol myristate acetate (PMA). Use of a reporter function, chloramphenicol acetyl transferase, controlled by 700 base pairs of the 5' flanking region of the NPY gene demonstrated that NGF and phorbol ester stimulated transcription of the NPY gene. This stimulation could be blocked by pre-incubating PC12 cells with calphostin C, a specific inhibitor of PKC. Our results indicate that NGF induces NPY gene expression via activation of PKC system. Although an increase in adenylate cyclase activity affects the expression of the NPY gene, activation of PKA appears not to be involved in mediating the NGF effects.
...
PMID:Role of protein kinase C in mediating NGF effect on neuropeptide Y expression in PC12 cells. 752 99

1. Neuropeptide Y (NPY; 10(-10)-10(-7) mol l-1) reduced basal short-circuit current (Isc) in a concentration-dependent manner in the rat distal colon but was ineffective in the proximal colon. 2. The action of NPY was dependent upon the presence of Cl- and HCO3- anions and was blocked by prior treatment of the tissue with a Cl- channel blocker. The decrease in Isc was associated with an increase in mucosa-to-serosa fluxes of Na+, Rb+ (K+) and Cl-, whereas the serosa-to-mucosa flux of Cl- was decreased. 3. The size of the inhibitory NPY effect was linearly correlated with the height of the basal Isc, i.e. it inhibited 55% of basal secretory Isc. 4. The action of NPY was unaffected by indomethacin and tetrodotoxin, when given alone, but was abolished, when the basal Isc was decreased to values near zero by a combination of both inhibitors. This inhibition could be overcome by restoring basal Isc with prostaglandin E2, indicating that the effect of NPY is not mediated by nerves or prostaglandins, but that NPY is only effective, when anion secretion is stimulated by the spontaneous release of neurotransmitters and prostaglandins. 5. NPY inhibited the increase in Isc induced by veratridine and prostaglandin E2, but it had no effect on the Isc induced by direct stimulation of the adenylate cyclase with forskolin, or on Isc induced by stimulation of the Ca(2+)-pathway with carbachol. Inhibition of the response to veratridine or prostaglandin E2 by NPY showed the same dependence on the height of the ISC just prior to addition of NPY as seen in control conditions, i.e. NPY inhibited 55% of cyclic AMP-mediated secretion.6. These results suggest that the effect of NPY is mediated by an inhibition of cyclic AMP-stimulated secretion, which is stimulated in the rat distal colon by a continuous release of prostaglandins and neurotransmitters.
...
PMID:The effect of neuropeptide Y on sodium, chloride and potassium transport across the rat distal colon. 758 5

Neuropeptide Y (NPY) exerts coronary vasomotor and inotropic effects on the canine heart. To test whether NPY also exerts regional myocardial electrophysiological effects, dose-response and time course changes resulting from intravenous and regional intracoronary infusions of NPY were obtained in 14 alpha-chloralose-anesthetized dogs. Under constant ventricular pacing, activation (A), recovery (R), and A-R interval (ARI) maps were constructed from multiplexed unipolar surface electrograms recorded simultaneously from 64 sites within a 1.6 x 1.6-cm left ventricular region. Effects were compared with those of vasoactive intestinal peptide (VIP) infusions and supramaximal left ansae subclaviae sympathetic nerve stimulation (SNS). The main finding was a uniform shortening of ARI, which reached a maximum of 8.7 +/- 1.2 ms, or 7% of control (P < 0.001), at about three times the baseline NPY plasma concentration (21.6 +/- 1.9 pg/ml). This effect decayed slowly (> 15 min) along with NPY plasma levels. The effect of similar VIP infusions and of SNS was 11%. Thus, compared with the previously identified maximal effect of adenylate cyclase activation (20%), exogenous NPY exerts a moderate but markedly sustained ventricular myocardial electrophysiological effect, which reaches maximum in relatively low plasma concentrations.
...
PMID:Myocardial electrophysiological effects of neuropeptide Y in dogs. 761 69

Neuropeptide Y has direct vasoconstrictor actions and potentiates the effects of other vasoconstrictor agents. To find out whether both effects of neuropeptide Y are mediated via the same receptor and intracellular mechanism, the interaction between neuropeptide Y and angiotensin II was studied in rabbit femoral arteries. In this preparation, neuropeptide Y, but not its 13-36 fragment, induced constriction. Only neuropeptide Y potentiated the vasoconstrictor response to angiotensin II and the associated rise in inositol-1-phosphate. These potentiating effects of neuropeptide Y were totally prevented by removal of extracellular Ca2+, partially prevented by a Ca(2+)-channel blocker and mimicked by a Ca(2+)-channel activator. Pharmacological modulation of adenylate cyclase had no effect. These results suggest that the direct and indirect vascular effects of neuropeptide Y are mediated via Y1 receptors and depend on the influx of extracellular Ca2+. The rise in inositol-1-phosphate seems to be secondary to an increase in intracellular Ca2+, while modulation of adenylate cyclase is apparently not involved.
...
PMID:Mechanism of interaction between neuropeptide Y and angiotensin II in the rabbit femoral artery. 771 50

Neuropeptide Y (NPY) content, NPY receptors, and alpha-subunits of the G proteins Go and Gi were determined in cerebral cortex of male normotensive Wistar-Kyoto and spontaneously hypertensive rats at 3-28 wk of age and of adult female rats. NPY lacked major effects on adenylate cyclase or inositol phosphate formation. NPY content was similar in all normotensive groups but lower in spontaneously hypertensive rats at all ages. 125I-NPY labeled a homogeneous population of Y1-like receptors. The Y1 NPY receptor number gradually increased with age with similar values in both strains but was significantly smaller in female than in male rats. The Y1 NPY receptor affinity was similar in all male groups but greater in female rats. The abundance of immunodetectable Go alpha and Gi alpha and of pertussis toxin substrates was less at 3 wk than in older rats but similar in both sexes and strains. We conclude that rat cerebral cortex contains Y1-like receptors; sex, age, and blood pressure differentially regulate NPY content, Y1 NPY receptors, and Go alpha and Gi alpha.
...
PMID:Regulation of NPY/NPY Y1 receptor/G protein system in rat brain cortex. 784 Mar 20


<< Previous 1 2 3 4 5 Next >>

---