Role of phosphoinositide turnover and cyclic AMP accumulation in prostaglandin-stimulated noradrenaline release from cultured adrenal chromaffin cells.
Prostaglandins (PGs) E1, E2 and F2 alpha stimulated release of noradrenaline from chromaffin cells; the most potent was PGF2 alpha with an EC50 of about 0.1 microM. The rank order of potency for release, and the EC50 for each PG, was the same as that for stimulation of (poly)phosphoinositide turnover. PGE1-stimulated release was dependent on extracellular calcium and sensitive to dihydropyridine calcium channel agonists and antagonists at 1 microM, but unlike release stimulated by 50 mM extracellular potassium was not sensitive to verapamil or diltiazem at 10 microM. The PGs also enhanced the turnover of inositol phospholipids, but the PGE1-stimulated formation of inositol phosphates was small compared to that produced by bradykinin, which stimulates a similar degree of release. Unlike release, the stimulation of inositol phosphate formation by PGs was not dependent on the addition of calcium to the medium. In down-regulation experiments, involving 2 hr preincubation with 30 microM PGE1, release in response to the three PGs was attenuated, whereas the release response to bradykinin and nicotine was unaffected. However, the stimulation of (poly)phosphoinositide turnover by PG was not down-regulated by prior exposure to PGE1. This dissociation of the inositol phosphate response suggests that release in response to PGs is not downstream of stimulation of inositol phospholipid hydrolysis. A further series of experiments is reported which shows that release is not a consequence of increased rate of cyclic AMP synthesis. It seems likely that PG stimulation of noradrenaline release is a result of calcium entry through dihydropyridine-sensitive channels by a mechanism independent of these two second messenger systems.
Plevin
R
R
Department of Pharmacology and Therapeutics, University of Leicester, England.
Owen
P J
PJ
Marriott
D B
DB
Jones
J A
JA
Boarder
M R
MR
D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002838:Chromaffin System / Q000187:drug effects* / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D009568:Nitrendipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000502:physiology*; D011453:Prostaglandins / Q000494:pharmacology*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011453:Prostaglandins; D005576:Colforsin; D009568:Nitrendipine; D000242:Cyclic AMP; D009638:Norepinephrine