Clonidine inhibits fluid absorption in the rabbit proximal convoluted renal tubule.
Previous studies have shown that norepinephrine (NE) and the beta-adrenoceptor agonist, isoproterenol (I), enhance fluid absorption (JV) in isolated, perfused proximal convoluted tubule segments (PCT). Pretreatment of PCT with the beta-adrenoceptor antagonist, propranolol, inhibited the action of NE and produced a significant decline in JV, suggesting modulation of JV by both alpha- and beta-adrenoceptors. The present studies further characterize the alpha-adrenoceptor control of JV in isolated perfused PCT using specific agonists and antagonists. Basal JV declined significantly with the addition of the alpha 2-adrenoceptor agonist, clonidine (10(-4) M), to the bath; however, it was unchanged with the addition of the alpha 1-adrenoceptor agonist, methoxamine (10(-6) or 10(-4) M). With the addition of 10(-6) M isoproterenol JV increased significantly, and returned to control values with the subsequent addition of clonidine (10(-6) or 10(-4) M). Pretreatment of PCT with the alpha 2-adrenoceptor antagonist, yohimbine (10(-5) M), or with pertussis toxin (100 ng/ml) did not interfere with the stimulation of JV by isoproterenol, but abolished the inhibition of isoproterenol-stimulated JV by clonidine. Thus, clonidine inhibits JV in PCT via an alpha 2-adrenoceptor. This effect is mediated by a pertussis toxin inhibitable GTP-binding protein, but not one that is coupled to adenylyl cyclase.
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Department of Medicine, Baylor College of Medicine, Houston, Texas.
Williams
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Suki
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D037361:Adenylate Cyclase Toxin; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D007687:Kidney Tubules, Proximal / Q000294:innervation* / Q000502:physiology; D037342:Pertussis Toxin; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D015016:Yohimbine; D037342:Pertussis Toxin; D003000:Clonidine