Kinin-induced relaxations of the rat duodenum.
Both bradykinin (BK) and des-Arg9-BK induced relaxations of the isolated longitudinal smooth muscles of the rat duodenum. No contractile effects were observed with both peptides at concentrations up to 1 mumol/l. Des-Arg9-BK was about 1000 times less potent than BK. The novel B2 antagonist HOE 140 (D-Arg-[Hyp3, Thi5, D-Phe7, Oic8]-BK) potently inhibited the BK-induced relaxations, but did not affect the relaxations induced by des-Arg9-BK. Conversely, the B1 receptor antagonist des-Arg9-[Leu8]-BK only inhibited des-Arg9-BK, but did not affect BK-induced relaxations. The relaxations induced by BK and by des-Arg9-BK were inhibited by apamin (1 mumol/l) demonstrating that apamin-sensitive K+ channels are involved. In contrast, tetraethylammonium (1 mmol/l) did not inhibit the relaxations. BK-induced relaxations were reduced by about 25% in the presence of indomethacin (10 mumol/l) although the concentration-response curve to BK was not shifted to the left. Prostaglandin E1 caused relaxations with a pD2 value of 9.2. It is concluded that both BK and des-Arg9-BK can elicit relaxations of the rat duodenum via pharmacologically distinct kinin receptor subtypes, but via similar effector mechanisms.
Griesbacher
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Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D004386:Duodenum / Q000187:drug effects*; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D011453:Prostaglandins; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D013757:Tetraethylammonium Compounds; D001030:Apamin; D019789:Tetraethylammonium; D001920:Bradykinin; D007213:Indomethacin