Morphine and anandamide coupling to nitric oxide stimulates GnRH and CRF release from rat median eminence: neurovascular regulation.
Nitric oxide (NO) is involved in neurohormonal secretion from median eminence neuroendocrine nerve terminals. We report that stimulation of NO release from median eminence fragments including vascular tissues occurs by mu3 receptor activation by morphine, or by cannabinoid type 1 receptor activation by anandamide. The released levels of NO are lower after anandamide than after morphine stimulation. These processes can be blocked by L-NAME, a specific nitric oxide synthase inhibitor, by naloxone for the morphine-stimulated NO release, or SR 141716A, a specific CB1 receptor inhibitor, for the anandamide-stimulated NO release. Furthermore, morphine and anandamide, by this NO dependent process, influences neurohormonal release from median eminence nerve terminals within 10 min. Via this NO dependent process, morphine stimulates both GnRH and CRF release, whereas anandamide selectively stimulates GnRH release. These observations together with previous data suggest that morphine and the anandamide-stimulated NO originates from the vascular endothelium of the portal plexus. These results indicate that endothelial cells of the median eminence may be involved in the release of neurohormones.
Prevot
V
V
INSERM, U422, Unité de Neuroendocrinologie et Physiopathologie Neuronale, place de Verdun, 59045 Lille Cedex, France.
Rialas
C M
CM
Croix
D
D
Salzet
M
M
Dupouy
J P
JP
Poulain
P
P
Beauvillain
J C
JC
Stefano
G B
GB
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D063388:Endocannabinoids; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D008297:Male; D008473:Median Eminence / Q000737:chemistry / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009490:Neurosecretory Systems / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D011957:Receptors, Opioid / Q000819:agonists / Q000502:physiology; D000077285:Rimonabant; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013047:Specific Pathogen-Free Organisms; D014666:Vasomotor System / Q000378:metabolism
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D009294:Narcotics; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D011957:Receptors, Opioid; C078711:enkephalin, delta-Ala(2)-Met(5)-; D009569:Nitric Oxide; D007987:Gonadotropin-Releasing Hormone; D004744:Enkephalin, Methionine; D009020:Morphine; D003346:Corticotropin-Releasing Hormone; D000077285:Rimonabant; C078814:anandamide; D019331:NG-Nitroarginine Methyl Ester