Barrel rotation in rats induced by intracerebroventricular bradykinin antagonists.
Intracerebroventricular (ICV) administration of bradykinin (BK) analogs containing the substitution DPhe7 produced extreme postural distortions within 2-4 min after injection, eventually causing rats to spin repeatedly around their longitudinal axis. This behavior, called barrel rotation, has been previously reported following ICV administration of several other neuropeptides. Episodes lasted 5-20 min; two deaths occurred at high doses, but no other long-term effects were observed. The quantal ED50 of the prototype compound B4162 (DArg0, Thi5,8 DPhe7BK), was 14.9 nmole; all seven other DPhe7 analogs tested elicited a positive response at 20 nmole. Among analogs not containing DPhe7, only BK elicited any activity (20% response rate), and only at 100 nmoles. Structure-activity considerations indicate that this behavior is not mediated by classical kinin receptors. The response rate to 20 nmole B4162 (81%) did not significantly change after pretreatment with ICV BK (100 nmoles), or IP atropine, haloperidol or phenytoin; whereas pretreatment with ICV captopril and muscimol and IP naloxone, diazepam and phenobarbital all significantly inhibited the response. A GABAergic mechanism may be involved in this peptide behavior.
Perry
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Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors*; D002216:Captopril / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009118:Muscimol / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D011187:Posture; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D009118:Muscimol; D009270:Naloxone; D010672:Phenytoin; D001285:Atropine; D002216:Captopril; D006220:Haloperidol; D003975:Diazepam; D001920:Bradykinin; D010634:Phenobarbital