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)

Effects of alpha adrenergic agents on intestinal secretion induced by prostaglandin E1 (PGE1), vasoactive intestinal peptide (VIP) and dibutyryl cyclic AMP (Bt2cAMP) were investigated in rat jejunum in vivo. Oxymetazoline and clonidine were more potent than epinephrine in inhibiting the PGE1-induced secretion. Methoxamine failed to inhibit the PGE1-induced secretion even with a 100-fold higher dose than that of clonidine. A high dose (1 mumol/kg) of oxymetazoline not only inhibited the PGE1- induced secretion but also enhanced net fluid absorption. Yohimbine reversed the inhibitory effect of clonidine, whereas phenoxybenzamine did not. These antagonists per se did not produce any effects on PGE1-induced secretion. Clonidine inhibited the intestinal secretion induced by VIP or Bt2cAMP, whereas methoxamine did not. The inhibitory effect of clonidine was reversed by yohimbine. Phenoxybenzamine per se inhibited intestinal secretion induced by either VIP or Bt2cAMP. Clonidine did not produce any significant effects on PGE1- augmented cAMP levels in jejunal mucosa in vivo. These results suggest that stimulation of alpha-2 adrenoceptors in rat jejunal mucosa inhibits some mechanisms distal to cAMP generation and in turn results in the inhibition of net water intestinal secretion. These findings also raise the question of general validity of a hypothesis that alpha-2 adrenoceptors regulate cellular functions through the inhibition of adenylate cyclase activity.
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PMID:Alpha-2 adrenergic inhibition of intestinal secretion induced by prostaglandin E1, vasoactive intestinal peptide and dibutyryl cyclic AMP in rat jejunum. 612 Oct 49

Three types of adrenergic receptors, beta, alpha-1, and alpha-2, were identified in human adipocytes, isolated from properitoneal adipose tissue, using both the binding of radioactive ligands and the effects of adrenergic agents on receptor-specific biochemical responses. Adrenergic binding studies showed the following results: [(3)H]dihydroalprenolol binding (beta adrenergic) B(max) 280 fmol/mg protein, K(D) 0.38 nM; [(3)H]para-aminoclonidine binding (alpha-2 adrenergic) B(max) 166 fmol/mg protein, K(D) 0.49 nM; [(3)H]WB 4101 binding (alpha-1 adrenergic) B(max) 303 fmol/mg protein, K(D) 0.86 nM. In adipocytes from subcutaneous adipose tissue, [(3)H]dihydroergocryptine binding indicated the presence of alpha-2 but not alpha-1 receptors. Beta and alpha-2 adrenergic receptors appeared to be positively and negatively coupled to adenylate cyclase, respectively. Cells or cell membranes were incubated with epinephrine (10 muM) alone and in combination with the antagonists yohimbine (alpha-2) and prazosin (alpha-1). Epinephrine alone prompted a modest increase in adenylate cyclase activity, cyclic AMP, and glycerol release, an index of lipolysis. Yohimbine (0.1 muM) greatly enhanced these actions whereas prazosin was without effect. The beta agonist, isoproterenol, stimulated glycerol release, whereas the alpha-2 agonist, clonidine, inhibited lipolysis and cyclic AMP accumulation. To assess further alpha-1 receptors, cells were incubated with [(32)P]phosphate and epinephrine (10 muM) alone and in combination with prazosin and yohimbine. Epinephrine alone caused a three- to fourfold increase in (32)P incorporation into phosphatidylinositol. Prazosin (0.1 muM) blocked this action whereas yohimbine (0.1 muM) was without effect. Thus, in a homogeneous cell preparation, the human adipocyte appears to have three different adrenergic receptors, each of which is coupled to a distinct biochemical response.
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PMID:Pharmacological characterizations of adrenergic receptors in human adipocytes. 625 62

The effect of the alpha adrenoceptor blocking agent yohimbine on cerebral dopamine metabolism has been investigated in the rat. Yohimbine (1 to 10 mg/kg i.p.) increased in both striatum and limbic areas 1) homovanillic acid and dihydroxyphenylacetic acid levels, 2) tyrosine hydroxylase activity measured in vitro, 3) the in vivo accumulation of dihydroxyphenylalanine after NSD 1015 and 4) the rate of dopamine disappearance after alpha-methyl-p-tyrosine. The inability of clonidine to prevent the yohimbine-induced enhancement of striatal homovanillic acid levels in doses that antagonize the yohimbine-induced increase in noradrenaline turnover as well as the failure of other alpha adrenoceptor blocking agents (tolazoline, phentolamine and prazosin) to increase dopamine metabolism suggest that alpha adrenoceptors are not involved in the yohimbine-induced alteration of dopamine metabolism. Similarly to neuroleptic agents, yohimbine reduced striatal acetylcholine concentrations and counteracted the dopamine (10(-5) M)-induced inhibition of the potassium-evoked release of [3H]acetylcholine from slices of caudate nucleus. Yohimbine failed to further enhance striatal homovanillic acid levels in animals pretreated with a supramaximal dose of haloperidol. Moreover, in rats treated with haloperidol for 10 days, the effect of yohimbine on striatal homovanillic acid and acetylcholine levels was markedly reduced. It is concluded that yohimbine possesses postsynaptic dopamine receptor blocking properties in addition to its ability to inhibit alpha adrenergic receptors. The failure of yohimbine to affect dopamine-sensitive adenylate cyclase activity in striatal homogenates suggests an action of the compound on the D2 receptor.
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PMID:Antidopaminergic properties of yohimbine. 719 14

We have used the in vitro preparation of the intact carotid body (CB) and isolated chemoreceptor cells to elucidate the distribution and function of alpha2-adrenoreceptors. The significance of the study lies in the fact that norepinephrine (NE), being the neurotransmitter of the sympathetic innervation to the CB, is also abundant in chemoreceptor cells. In intact CB whose catecholamine (CA) deposits had been labeled by prior incubation with the CA precursor [3H]tyrosine, the alpha2-antagonist yohimbine (10 microM) potentiated the low-PO2 (33 and 60 mmHg)-induced release of [3H]CA by 100 and 53%, respectively. Yohimbine (10 microM) and SKF-86466 (50 microM; another alpha2-antagonist) reversed the inhibition of the release of [3H]CA produced by the alpha2-receptor agonists clonidine and UK-14304 (10 microM). The increase in adenosine 3',5'-cyclic monophosphate produced by low PO2 was further augmented by yohimbine and nearly halved by UK-14304 and clonidine. In isolated chemoreceptor cells, UK-14304 and NE inhibited voltage-dependent Ca2+ currents by 28 and 32%, respectively. These results indicate that alpha2-receptors are present in chemoreceptor cells, where they reduce the release of [3H]CA. Inhibition of adenylate cyclase(s) and Ca2+ channels may be involved in this effect. Using intact CB from normal and chronically sympathectomized animals, we demonstrated a specific accumulation of [3H]NE in intraglomic sympathetic endings. Hypoxia (PO2 approximately 33 mmHg) did not elicit release of [3H]NE from the sympathetic endings, but high extracellular K+ (K+(e)) induced a release of [3H]NE that was inhibited by alpha2-agonists and augmented by alpha2-antagonists. These findings demonstrate that alpha2-receptors are also present in the sympathetic endings of the CB, where they modulate the release of NE. As a whole, this work provides a more detailed understanding of the role of the sympathetic innervation in the control of the CB chemoreceptor function, including the cellular mechanisms of the action of NE.
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PMID:Mechanisms of alpha2-adrenoceptor-mediated inhibition in rabbit carotid body. 912 7

1. Forskolin, an activator of adenylate cyclase, potentiated the relaxing response to isoproterenol in rabbit aortic rings precontracted by phenylephrine (PE). 2. The potentiating effect of forskolin was inhibited by propranolol, a beta-adrenoceptor inhibitor, but not by methylene blue, a guanylate cyclase inhibitor. 3. The relaxing response to terbutaline, a beta 2-adrenoceptor agonist, but not lower concentrations of dobutamine, a beta 1-adrenoceptor agonist, also was potentiated by forskolin. Forskolin, however, potentiated the relaxing response to high concentrations of dobutamine, which activates both beta 1- and beta 2-adrenoceptors. 4. Yohimbine, an alpha 2-adrenoceptor inhibitor, glyburide, an ATP-sensitive K+ channel inhibitor, iberiotoxin, a Ca(2+)-activated K+ channel inhibitor, or endothelium-removal failed to affect the potentiating effect of forskolin. 5. Dibutyryl cyclic AMP (cAmp) also potentiated the relaxing response to terbutaline. 6. These results suggest that in rabbit aortic rings forskolin causes the apparent potentiation of isoproterenol-induced relaxation by mainly affecting the relaxing response due to the activation of beta 2-adrenoceptors by the forskolin-induced increase in the level of cAMP.
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PMID:Potentiation of the relaxing action of isoproterenol by forskolin in rabbit aortic rings: the involvement of beta 2-adrenoceptors. 918 14

The detailed mechanisms underlying morphine-signaling pathways in platelets remain obscure. Therefore, we systematically examined the influence of morphine on washed human platelets. In this study, washed human platelet suspensions were used for in vitro studies. Furthermore, platelet thrombus formation induced by irradiation of mesenteric venules with filtered light in mice pretreated with fluorescein sodium was used for an in vivo thrombotic study. Morphine concentration dependently (0.6, 1, and 5 microM) potentiated platelet aggregation and the ATP release reaction stimulated by agonists (i.e., collagen and U46619) in washed human platelets. Yohimbine (0.1 microM), a specific alpha(2)-adrenoceptor antagonist, markedly abolished the potentiation of morphine in platelet aggregation stimulated by agonists. Morphine also potentiated phosphoinositide breakdown and intracellular Ca(2+) mobilization in human platelets stimulated by collagen (1 microg/ml). Moreover, morphine (0.6-5 microM) markedly inhibited prostaglandin E(1) (10 microM)-induced cyclic AMP formation in human platelets, while yohimbine (0.1 microM) significantly reversed the inhibition of cyclic AMP by morphine (0.6 and 1 microM) in this study. The thrombin-evoked increase in pH(i) was markedly potentiated in the presence of morphine (1 and 5 microM). Morphine (2 and 5 mg/g) significantly shortened the time require to induce platelet plug formation in mesenteric venules. We concluded that morphine may exert its potentiation in platelet aggregation by binding to alpha(2)-adrenoceptors in human platelets, with a resulting inhibition of adenylate cyclase, thereby reducing intracellular cyclic AMP formation followed by increased activation of phospholipase C and the Na(+)/H(+) exchanger. This leads to increased intracellular Ca(2+) mobilization, and finally potentiation of platelet aggregation and of the ATP release reaction.
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PMID:Morphine-potentiated platelet aggregation in in vitro and platelet plug formation in in vivo experiments. 1271 56


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