Rauwolscine induces contraction in the dog mesenteric artery precontracted with KCl and endothelin-1: mediation via 5-hydroxytryptamine1-like receptors.
Rauwolscine, a selective alpha-2 adrenoceptor antagonist, elicited a sustained contraction in the dog mesenteric artery precontracted with 20 mM KCl or 10(-9) M endothelin-1. Cumulative concentration-response curves to rauwolscine were not shifted by spiperone, propranolol, pindolol, mianserin, ketanserin, prazosin or phenoxybenzamine at the concentration of 10(-6) M. The pA2 values against rauwolscine were 8.34 +/- 0.32 for methysergide, 8.52 +/- 0.22 for methiothepin and 5.84 +/- 0.27 for phentolamine, which were in good agreement with the pA2 values for those antagonists against 5-hydroxytryptamine (5-HT) in the dog mesenteric artery precontracted with 20 mM KCl. Contractile responses to 5-HT after pretreatment with 20 mM KCl were antagonized in an apparently competitive manner by 10(-5) M rauwolscine. In the absence of precontraction, rauwolscine also shifted 5-HT-induced contractions in a parallel manner. These data suggest that rauwolscine is a partial agonist with a lower intrinsic activity than 5-HT and acts at the same 5-HT1-like receptors as 5-HT, most probably 5-HT1D receptors, in the dog mesenteric artery precontracted with KCl.
Shimamoto
Y
Y
Department of Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Shimamoto
H
H
Kwan
C Y
CY
Daniel
E E
EE
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004347:Drug Interactions; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D016232:Endothelins; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D010656:Phenylephrine; D015016:Yohimbine; D012701:Serotonin; D011189:Potassium Chloride; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin