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)

Arterial relaxant responses to beta adrenoceptor agonists are decreased in spontaneously hypertensive rats (SHR) when compared with normotensive Wistar-Kyoto rats (WKY). To determine which component of the beta adrenoceptor-adenylate cyclase (AC) system is involved in the decreased beta adrenoceptor responses, effects of two activators of AC-forskolin and cholera toxin and of dibutyryl cyclic AMP (DBcAMP) were compared between the strips of femoral arteries isolated from 13-week-old SHR and age-matched WKY. Arterial relaxant responses to either forskolin, an activator of AC or DBcAMP were not significantly different between the SHR and WKY, whereas the relaxant responses to norepinephrine (NE) via beta adrenoceptors were significantly weaker in the SHR than in the WKY. In the absence of timolol, a beta adrenoceptor antagonist, contractile responses to NE were significantly greater in the SHR than in the WKY. Timolol augmented the contractile responses to NE to a greater extent in the WKY than in the SHR. After the blockade by timolol of beta adrenoceptors, contractile responses to alpha adrenoceptor stimulation with NE were not significantly different between the two strains. The pretreatment of the strips with cholera toxin, an activator of stimulatory GTP-binding protein (Gs), antagonized the alpha adrenoceptor-mediated contractions much greater in the WKY than in the SHR. The alpha adrenoceptor-mediated contractions after the pretreatment with cholera toxin were comparable to the contractile responses to NE determined in the absence of timolol in either the SHR or the WKY. Forskolin and DBcAMP also antagonized the alpha adrenoceptor-mediated contractions. However, these antagonisms were not significantly different between the two strains. The cellular cAMP content in arterial strips after the stimulation with NE was significantly less in the SHR than in the WKY, whereas the cAMP contents were similar in arterial strips from both strains which were stimulated with forskolin. These results suggest that the reduced function of Gs is involved in the abnormality of beta adrenoceptor-AC system in the SHR femoral artery.
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PMID:Reduced function of the stimulatory GTP-binding protein in beta adrenoceptor-adenylate cyclase system of femoral arteries isolated from spontaneously hypertensive rats. 245 80

1. Arterial relaxant responses to beta-adrenoceptor agonists are decreased in spontaneously hypertensive rats (SHR) when compared with normotensive Wistar-Kyoto rats (WKY). To establish which component of the beta-adrenoceptor.adenylate cyclase (AC) system is impaired in the SHR arteries, effects of two activators of AC--cholera toxin (CTX) and forskolin--and of dibutyryl cyclic AMP (db cyclic AMP) were compared between strips of femoral arteries isolated from 13 week-old SHR and age-matched WKY. 2. In the absence of timolol, a beta-adrenoceptor antagonist, contractile responses of the strips to noradrenaline (NA) were significantly greater in the SHR than in the WKY. Timolol augmented the contractile responses to NA to a smaller extent in the SHR than in the WKY. 3. After blockade by timolol of beta-adrenoceptors, contractile responses of the strips to NA through the activation of alpha-adrenoceptors were not significantly different between the two strains. 4. Pre-treatment of the strips with CTX, an activator of the stimulatory GTP-binding protein (Gs), produced a slow-onset and long-lived antagonism of the alpha-adrenoceptor-mediated contractions. The antagonism was much smaller in the SHR than in the WKY. 5. The dose-response curves of the strips from both strains for alpha-adrenoceptor stimulation with NA determined after pretreatment with CTX were comparable to those determined in the absence of timolol. 6. Forskolin, an activator of the catalytic subunit of AC, and DB cyclic AMP also antagonized the alpha-adrenoceptor-mediated contractions. However, these antagonisms were not significantly different between the two strains. 7. Isobutyl methylxanthine (IBMX), an inhibitor of cyclic AMP phosphodiesterase, produced a similar antagonism of the alpha-adrenoceptor-mediated contractions between the two strains. 8. These results suggest that a reduced function of Gs is the main factor responsible for the decreased responsiveness to beta-adrenoceptor stimulation in the SHR femoral artery.
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PMID:Role of stimulatory GTP-binding protein (Gs) in reduced beta-adrenoceptor coupling in the femoral artery of spontaneously hypertensive rats. 246 85

The hypotensive effect of different adrenergic agonists and antagonists were screened both in normo- and hypertensive rabbit eyes. The drugs were applicated topically and intraocular pressure (IOP) was monitored constantly with a manometric method. Subsequently the inhibitory effect of the antagonists on isoproterenol-stimulated adenylate cyclase activity in the ciliary processes was analyzed in vitro. In normotensive eyes agonist isoproterenol (beta) and antagonists labetalol (alpha beta), metoprolol (beta 1) and acebutolol (beta 1) decreased significantly IOP. In hypertensive eyes only isoproterenol and labetalol decrease IOP markedly. Timolol (beta) did not decrease IOP, although it inhibited adenylate cyclase activity as actively as labetalol. The other antagonists showed no inhibitory effect on in this respect. The results indicated that alpha-activity (labetalol, alpha beta) seems to potentiate the beta-activity (timolol, beta) in decreasing IOP. Whether this alpha-effect is a presynaptic effect (adrenergic denervation destroys it) is not yet clear. Similarly the beta 1-effect (metoprolol), without affecting adenylate cyclase activity, decreased IOP as well. This might be due to pre-synaptic release of endogenous transmitter(s) which in turn stimulate post-synaptic adenylate cyclase and induce the decreased IOP. Besides this, the possible role of blood vessels and CNS must also be kept in mind.
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PMID:Comparison of the effects of adrenergic agonists and alpha-, beta 1-, beta 2-antagonists on the intraocular pressure and adenylate cyclase activity in the ciliary processes of the rabbit. 285 30

Retinal pigment epithelial (RPE) cell migration has been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR). Using a modified Boyden chamber assay, we have examined the effect of cyclic nucleotides on human RPE cell migration in vitro. Dibutyryl cyclic 3',5'-adenosine monophosphate (cAMP) (10(-3) mmol/L) inhibits RPE cell random migration by 83%, fibronectin-induced chemotaxis by 61%, and platelet-derived growth factor-induced chemotaxis by 68%. Random and directed migration of RPE cells is not significantly affected by 8-bromo cyclic 3',5'-guanosine monophosphate. Agents that significantly increase intracellular levels of cAMP are also inhibitors of RPE cell migration. Though there is a fairly good correlation for most drugs for their ability to stimulate cAMP production and their ability to inhibit cell migration, it is not perfect, suggesting that some drugs may modulate migration by more than one mechanism. Timolol blocked both the isoproterenol-induced stimulation of RPE adenylate cyclase and attenuated the ability of isoproterenol to inhibit RPE migration. These data suggest that cAMP may modulate RPE cell migration in an inhibitory fashion. Elucidation of the biochemical events involved in RPE cell migration could provide information that might be useful in planning a strategy to attempt pharmacologic control of proliferative vitreoretinopathy.
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PMID:Cyclic 3',5'-adenosine monophosphate modulates retinal pigment epithelial cell migration in vitro. 302 98

Using a modified Boyden chamber assay, we have examined the effect of cyclic nucleotides on bovine aortic endothelial cell migration in vitro. Dibutyrl cyclic 3',5'-adenosine monophosphate (5 mM) inhibited endothelial cell random migration by 67% and inhibited fibronectin-induced chemotaxis by 75%. Agents which significantly stimulated adenylate cyclase activity in endothelial cell membranes were also effective inhibitors of endothelial cell migration. Timolol blocked both the isoproterenol-induced stimulation of adenylate cyclase and the ability of isoproterenol to inhibit endothelial cell migration. Caffeine and isoproterenol together had a greater inhibitory effect on endothelial cell motility than either alone. These data suggest that cAMP may modulate vascular endothelial cell migration in an inhibitory fashion.
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PMID:Cyclic 3',5'-adenosine monophosphate modulates vascular endothelial cell migration in vitro. 303 75