Role of MC4 receptors in the depressor and bradycardic effects of alpha-MSH in the nucleus tractus solitarii of the rat.
The receptor subtype(s) responsible for the cardiovascular actions of the melanocortins remains to be elucidated. This study investigated the cardiovascular effects of central injection of alpha-MSH and a potent cyclic MC3/4 receptor agonist, MTII, in the presence and absence of the newly developed MC4 receptor selective antagonist, HS014. Both alpha-MSH (250 pmol) and MTII (20-500 pmol) produced a rapid decrease in blood pressure and heart rate after injection into the nucleus tractus solitarii (NTS) of urethane-anaesthetised male Sprague-Dawley rats. These responses were attenuated in a dose-dependent manner by prior local NTS blockade with HS014 (20 or 100 pmol), providing evidence for the role of the MC4 receptor in the cardiovascular changes following NTS injection of melanocortins in the rat.
Pavia
Jillian M
JM
Department of Neuroscience, Division of Pharmacology, Uppsala University, Sweden.
Schiöth
Helgi B
HB
Morris
Margaret J
MJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced*; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008845:Microinjections; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017552:Solitary Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D000521:alpha-MSH / Q000494:pharmacology*
C116941:HS014 cyclic peptide; D010456:Peptides, Cyclic; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D000521:alpha-MSH