Neuropeptide Y inhibits beta-adrenergic agonist- and vasoactive intestinal peptide-induced cyclic AMP accumulation in rat pinealocytes through pertussis toxin-sensitive G protein.
The effects of neuropeptide Y (NPY) on pineal gland cyclic AMP (cAMP) accumulation were investigated using dispersed pinealocytes from rats. NPY inhibited the intracellular cAMP accumulation stimulated by isoproterenol and norepinephrine in a dose-dependent manner during a 10-min incubation of pinealocytes. NPY (1 x 10(-7) M) also inhibited vasoactive intestinal peptide (VIP)- and cholera toxin-induced cAMP accumulation. The inhibitory effect of NPY on isoproterenol-induced cAMP accumulation was completely abolished by a 5-h pretreatment of pinealocytes with 1 microgram/ml of pertussis toxin (PT). These results suggest that NPY participates in modulation of cAMP production in the rat pineal gland through PT-sensitive G protein. Yohimbine, an alpha 2-adrenergic antagonist, blocked NPY inhibition of isoproterenol-stimulated cAMP accumulation. On the other hand, the alpha 2-adrenergic agonist clonidine by itself did not affect cAMP accumulation stimulated by isoproterenol but significantly potentiated NPY action. The present study demonstrates that NPY inhibits beta-adrenergic or VIPergic stimulation of the pineal gland cAMP accumulation. The inhibitory effect of NPY is mediated through PT-sensitive G protein. Our results also suggest that NPY exerts its action to affect alpha 2-adrenoceptor function.
Third Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Y
Y
Harada
M
M
Okubo
K
K
Yaga
T
T
Kaneko
K
K
Kaku
D000318:Adrenergic beta-Agonists / Q000037:antagonists & inhibitors*; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D010870:Pineal Gland / Q000166:cytology* / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D009478:Neuropeptide Y; D010566:Virulence Factors, Bordetella; D015016:Yohimbine; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D009638:Norepinephrine; D011224:Prazosin