A hypotensive and bradycardic action of gamma 2-melanocyte-stimulating hormone (gamma 2-MSH) microinjected into the nucleus tractus solitarii of the rat.
In conscious and urethane-anesthetized rats intravenously (i.v.) administered gamma 2-melanocyte-stimulating hormone (gamma 2-MSH), a melanotropin derived from the precursor peptide pro-opiomelanocortin (POMC), has been shown to induce a pressor response combined with a tachycardia. A site of action within the hindbrain, e.g. the nucleus tractus solitarii (NTS) or the area postrema (AP), has been suggested. In order to test the postulate that gamma 2-MSH acts within these hindbrain regions, the peptide was microinjected into various parts of the NTS and into the AP of urethane-anesthetized rats and blood pressure (BP) and heart rate (HR) were measured. Injection of gamma 2-MSH (100-500 pmol) into the NTS resulted in a dose-dependent decrease in BP and HR rather than in the expected pressor and tachycardiac response which is generally found in conscious and urethane-anesthetized rats following i.v. administration of the peptide. With respect to the depressor and bradycardiac effect the melanotropin was far more potent when injected into the pars commissuralis than into the medial part of the NTS. The responses were maximal after 3-4 min and lasted for about 15 min. gamma 2-MSH had no effect when injected into the AP. It is noteworthy that also a hypotensive and bradycardic effect for gamma 2-MSH is found in pentobarbital-anesthetized rats following i.v. administration. Therefore, we conclude that in addition to a pressor and tachycardic response gamma 2-MSH can elicit an opposite effect by interaction with structures within a discrete region in the NTS, the pars commissuralis.(ABSTRACT TRUNCATED AT 250 WORDS)
De Wildt
D J
DJ
Department of Medical Pharmacology, Rudolf Magnus Institute, Medical Faculty, Utrecht University, The Netherlands.
Van der Ven
J C
JC
Van Bergen
P
P
De Lang
H
H
Versteeg
D H
DH
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced*; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced*; D007275:Injections, Intravenous; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D008845:Microinjections; D010424:Pentobarbital; D051381:Rats; D017208:Rats, Wistar; D017552:Solitary Nucleus / Q000187:drug effects* / Q000502:physiology; D014520:Urethane
D014520:Urethane; D009074:Melanocyte-Stimulating Hormones; D010424:Pentobarbital