Alpha-MSH and gamma-MSH modulate early release of hypothalamic PGE2 and NO induced by IL-1beta differently.
Interleukin-1beta (IL-1beta) stimulates corticotropin-releasing hormone (CRH) secretion in hypothalamus, which involves the release of prostaglandins (PGE2) and nitric oxide (NO). We have demonstrated that melanocortins can inhibit the early effects of IL-1beta on the HPA axis by acting on the central nervous system (CNS). Our study investigated whether alpha-melanocyte stimulating hormone (alpha-MSH) and gamma-MSH could inhibit IL-1beta-induced PGE2 and NO release in hypothalamus in the rapid activation of the HPA axis. An i.c.v. injection of 12.5 ng/microl of IL-1beta significantly increased the release of PGE2 and NOS activity in the hypothalamus. Treatment with alpha-MSH (0.1 microg/microl) inhibited the effect of IL-1beta on PGE2 release. Also, gamma-MSH (1 microg/microl) eliminated the increase in NOS activity induced by IL-1beta. Our data indicate the modulatory role of melanocortins in the early hypothalamic response to IL-1beta, with different regulation of PGE2 and NO release.
Cragnolini
Andrea Beatriz
AB
Departamento Farmacología, Facultad de Ciencias Químicas, UNC., Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000 Córdoba, Argentina.
Caruso
Carla
C
Lasaga
Mercedes
M
Scimonelli
Teresa Nieves
TN
D000818:Animals; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D053583:Interleukin-1beta / Q000008:administration & dosage*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000521:alpha-MSH / Q000008:administration & dosage*; D019825:gamma-MSH / Q000008:administration & dosage*
D004338:Drug Combinations; D053583:Interleukin-1beta; D019825:gamma-MSH; D009569:Nitric Oxide; D000521:alpha-MSH; D015232:Dinoprostone