Role of phosphodiesterase and protein kinase G on nitric oxide-induced inhibition of prolactin release from the rat anterior pituitary.
OBJECTIVE
In order to determine the mechanism by which nitric oxide (NO) inhibits prolactin release, we investigated the participation of cGMP-dependent cAMP-phosphodiesterases (PDEs) and protein kinase G (PKG) in this effect of NO.


METHODS
Anterior pituitary glands of male rats were incubated with inhibitors of PDE and PKG with or without sodium nitroprusside (NP). Prolactin release, and cAMP and cGMP concentrations were determined by RIA.


CONCLUSIONS
The inhibitory effect of NP (0.5 mmol/l) on prolactin release and cAMP concentration was blocked by EHNA (10(-4)mol/l) and HL-725 (10(-4)mol/l), inhibitors of cGMP-stimulated cAMP-PDE (PDE2). 8-Br-cGMP (10(-4) and 10(-3)mol/l), which mimics cGMP as a mediator of NP effects on prolactin release, also decreased cAMP concentration. Zaprinast (10(-4)mol/l), a selective inhibitor of specific cGMP-PDE (PDE5), potentiated the NP effect on cAMP concentration. Rp-8-[(4-chlorophenyl)thio]-cGMP triethylamine (Rp-8-cGMP, 10(-7)-10(-6)mol/l), an inhibitor of PKG, reversed the effect of NP on prolactin release. The present study suggests that several mechanisms are involved in the inhibitory effect of NO on prolactin release. The activation of PDE2 by cGMP may mediate the inhibitory effect of NO on cAMP concentration and therefore on prolactin release. NO-activated PKG may also be participating in the inhibitory effect of NO on prolactin release.
Centro de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
M O
MO
Velardez
A
A
De Laurentiis
M
M
del Carmen Díaz
M
M
Lasaga
D
D
Pisera
A
A
Seilicovich
B H
BH
Duvilanski
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D011688:Purinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D011388:Prolactin; D000242:Cyclic AMP; D011494:Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast; D006152:Cyclic GMP