Nitric oxide, interleukin and prostaglandin interactions affecting the magnocellular system.
Magnocellular neurons are innervated by an excitatory histaminergic pathway. They also express neuronal NO synthase, interleukin-1beta (IL-1beta) and cyclo-oxygenase (COX). In normally hydrated rats when NO synthase activity is inhibited with N(G)-nitro-L-arginine methyl ester (L-NAME), administered intracerebroventricularly (i.c.v.), OT concentration in plasma increases. In the present study, the increase in hormone after L-NAME is attenuated by indomethacin, an inhibitor of COX, as well as by antagonists of histamine receptors at H1 (pyrilamine) and H2 (cimetidine) subtypes injected i.c.v. Moreover, enhanced OT secretion induced by centrally administered IL-1beta, but not naloxone (opiate receptor antagonist), is prevented by indomethacin. PGE2 and PGD2 (i.c.v.) stimulate OT release, but only PGD2 affects circulating vasopressin levels. Thus, NO inhibits release of OT stimulated by: (1) a COX-dependent mechanism, i.e. NO-->-(COX-->+PG-->+OT release); (2) histamine, i.e. NO-->-(histamine-->H1 and H2 receptors-->+OT release); and possibly (3) IL-1beta, i.e. NO-->-(IL-1beta-->+COX-->+PG-->+OT release). These interactions of NO, cytokine and histamine may be important for management of stress-induced activation of neuroendocrine systems.
Summy-Long
Joan Y
JY
Department of Pharmacology-MCH108, The Pennsylvania State University, The Milton S. Hershey Medical Center, P.O. Box 850, Hershey, PA 17033, USA. jsl2@psu.edu
Bui
Vuong
V
Gestl
Shelley
S
Kadekaro
Massako
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage; D006635:Histamine H2 Antagonists / Q000008:administration & dosage; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D009994:Osmolar Concentration; D010121:Oxytocin / Q000097:blood; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014667:Vasopressins / Q000097:blood; D014868:Water Deprivation / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007375:Interleukin-1; D007378:Interleukins; D009292:Narcotic Antagonists; D011453:Prostaglandins; D014667:Vasopressins; D009569:Nitric Oxide; D010121:Oxytocin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D011451:Prostaglandin-Endoperoxide Synthases; D019331:NG-Nitroarginine Methyl Ester