title: Possible involvement of beta endorphin(1-31) and dynorphin(1-13) in the central hypotensive mechanism of action of alpha methyldopa.
abstract: The present study was performed to gain more information on the nature of the opioid peptide(s) involved in the mechanism of action of alpha-methyldopa. Conscious, normotensive Wistar rats were used and all treatments were given intracisternally. For blood pressure and heart rate, pretreatment with a midportion beta-endorphin antiserum resulted in a parallel shift to the right of the dose-response curve for alpha-methyldopa. In addition, when rats were pretreated with various dilutions of this antiserum and treated with a constant dose of alpha-methyldopa, the antiserum dose-dependently inhibited alpha-methyldopa-induced hypotension and bradycardia. Using antisera specifically recognizing the C-terminus of beta-, gamma- and alpha-endorphin, respectively, revealed that only the beta-endorphin antiserum inhibited the decrease in blood pressure seen after administration of alpha-methyldopa. An antiserum against [Met5]enkephalin did not influence the cardiovascular responses following alpha-methyldopa. On the other hand, a dynorphin(1-13) antiserum also inhibited in a dose-dependent manner the hypotension induced by alpha-methyldopa. When administered 3 h after the injection of alpha-methyldopa, the beta-endorphin and dynorphin(1-13) antisera failed to reverse the hypotension induced by alpha-methyldopa. The results favor a role for beta-endorphin(1-31) and dynorphin(1-13) in the hypotension centrally mediated by alpha-methyldopa.
authors.affiliation: Rudolf Magnus Institute for Pharmacology, Medical Faculty, State University of Utrecht, The Netherlands.
authors.forename: P L
authors.initials: PL
authors.lastname: van Giersbergen
authors.forename: V M
authors.initials: VM
authors.lastname: Wiegant
authors.forename: W
authors.initials: W
authors.lastname: de Jong
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002946:Cisterna Magna; D004399:Dynorphins / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007267:Injections; D008297:Male; D008750:Methyldopa / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D010446:Peptide Fragments; D008750:Methyldopa; D001615:beta-Endorphin; C026843:dynorphin (1-13); D004399:Dynorphins