Prostaglandins of the E Series Stimulate Cyclic AMP Accumulation and N‐Acetylation of Serotonin in Chick Pineal Cells

Abstract

We investigated the effects of prostaglandins on cyclic AMP (cAMP) levels and on the activity of the rate-limiting enzyme of melatonin biosynthesis, arylalkylamine-N-acetyltransferase (NAT). The study was performed on primary cultures of dispersed chick pineal cells. Prostaglandin E, (PGE,) increased cAMP levels 2-fold and this stimulation went up to 4-fold in the presence of a phosphodiesterase inhibitor. The PGE,- evoked increase in cAMP levels did not desensitize over 6 h. The potency order of a series of prostaglandins to increase cAMP levels (PGE(1) PGE(1) >PGA2>PGD(2) ≃PGF(2) α) agreed with the pharmacological profile of the adenylate cyclase-coupled prostaglandin receptor. Inhibition of endogenous prostaglandin synthesis by two cyclooxygenase inhibitors (indomethacin and aspirin) caused a 30% decrease in cAMP levels. This effect was completely reversed by the addition of exogenous PGE(1) or PGE(2) . Indomethacin and aspirin also caused a 50% decrease in NAT activity. Prostaglandins of the E series increased NAT activity up to 2-fold above basal level and restored NAT activity after inhibition by indomethacin or aspirin. These results are the first illustration of a role for prostaglandins in chick pineal cells. The correlations observed between cAMP levels and NAT activity suggest that the regulation of NAT activity by prostaglandins of the E series might be mediated by changes in cAMP concentration.