Central alpha-melanocyte-stimulating hormone acts at melanocortin-4 receptor to activate sympathetic nervous system in conscious rabbits.
Intracerebroventricular injection of alpha-melanocyte-stimulating hormone (alpha-MSH) elicited increases in arterial pressure and renal sympathetic nerve activity in conscious rabbits. Pretreatment with intracerebroventricular injection of agouti-related protein, an endogenous melanocortin-3 and 4 receptor antagonist, prevented cardiovascular and sympathetic responses to alpha-MSH. Pretreatment with intracerebroventricular injection of JKC-363, a synthetic specific melanocortin-4 receptor antagonist, also prevented cardiovascular and sympathetic responses to alpha-MSH. In contrast, intravenous alpha-MSH (1 nmol) failed to cause any cardiovascular responses. These results suggest that intracerebroventricularly administered alpha-MSH acts at the melanocortin-4 receptor in the brain and activates sympathetic outflow, resulting in an increase in arterial pressure.
Matsumura
Kiyoshi
K
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 12-8582, Japan. matsumk@intmed2.med.kyushu-u.ac.jp
Tsuchihashi
Takuya
T
Abe
Isao
I
Iida
Mitsuo
M
D054369:Agouti-Related Protein; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects; D003243:Consciousness / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D011506:Proteins / Q000494:pharmacology; D011817:Rabbits; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000187:drug effects / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D000521:alpha-MSH / Q000494:pharmacology*
D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D000521:alpha-MSH