Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Effects of adenosine 3':5'-cyclic monophosphate (cyclic AMP)-affecting agents were compared in mesenteric and renal resistance arteries that had been isolated from 20 week old Wistar-Kyoto rats, chemically sympathectomized, stretched to their optimal diameter for mechanical performance and made to contract in response to 30 mM potassium. 2. In mesenteric resistance arteries, isoprenaline, dopamine, NaF, forskolin, isobutyl-methylxanthine, milrinone and dibutyryl-cyclic AMP induced relaxation. Clonidine induced further increases in tension that could be reduced by pertussis toxin and prazosin but not by yohimbine. Clonidine also reduced relaxant responses to isoprenaline. 3. In renal resistance arteries, isoprenaline and dopamine failed to induce relaxation. Compared to mesenteric resistance arteries, renal vessels were less sensitive to the relaxant effect of NaF, forskolin and isobutyl-methylxanthine. Relaxant responses to dibutyryl-cyclic AMP did not differ between the two resistance arteries. 4. Indirect evidence thus suggests that in mesenteric resistance arteries, adenylate cyclase is susceptible to pharmacological activation and inhibition and is functionally coupled to relaxation. The refractory nature of renal resistance arteries to the relaxant effects of isoprenaline and dopamine could be due primarily to absence of appropriate receptors and to a relatively low activity of adenylate cyclase.
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PMID:Effects of cyclic AMP-affecting agents on contractile reactivity of isolated mesenteric and renal resistance arteries of the rat. 170 6

This study examines the action of the beta(3)-adrenoceptor antagonist SR59230A [3-(2-ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanoloxalate] at cloned mouse beta(3)-adrenoceptors expressed in Chinese hamster ovary cells (CHO-K1-beta(3)) or endogenously expressed in 3T3-F442A adipocytes or ileum. SR59230A displayed partial agonist properties compared with the beta(3)-adrenoceptor agonist CL316243 [(R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]-propyl]1,3-benzodioxole-2,2-dicarboxylate] in CHO-K1-beta(3) with the intrinsic activity increasing with the level of receptor expression. Functional affinity values for SR59230A at each level of receptor expression were in agreement with pK(I) values determined by binding. In cytosensor microphysiometer studies, SR59230A was a full agonist for increases in extracellular acidification rates (ECARs) at all levels of receptor expression, and antagonist actions were measurable only in medium- or low-expressing cells. In 3T3-F442A adipocytes, SR59230A antagonized CL316243-mediated increases of cAMP and had no agonist actions. However, in the cytosensor micro-physiometer, SR59230A (acting via beta(3)-adrenoceptors) was an agonist with an intrinsic activity greater than CL316243. In mouse ileum, SR59230A relaxed smooth muscle, although concentration-response curves were biphasic. Relaxant effects were produced by concentrations that did not affect cAMP levels. Differences in tissue responses to SR59230A were not caused by major differences in expression of Galphas. ECAR responses were not affected by pretreatment of cells with pertussis toxin, indicating that signaling did not involve Gi. Therefore, SR59230A displays agonist and antagonist actions at the mouse beta(3)-adrenoceptor. Because SR59230A only antagonized accumulation of cAMP in 3T3-F442A adipocytes yet in the same cells was an agonist for ECAR, cAMP-independent signaling pathways must mediate part of the agonist actions in the microphysiometer.
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PMID:Evidence for pleiotropic signaling at the mouse beta3-adrenoceptor revealed by SR59230A [3-(2-Ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanol oxalate]. 1557 84