Role of phosphoinositide turnover and cyclic AMP accumulation in prostaglandin-stimulated noradrenaline release from cultured adrenal chromaffin cells

R. Plevin, P. J. Owen, D. B. Marriott, J. A. Jones, M. R. Boarder

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Prostaglandins (PGs) E1, E2 and F(2α) stimulated release of noradrenaline from chromaffin cells; the most potent was PGF(2α) with an EC50 of about 0.1 μM. 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 μM, but unlike release stimulated by 50 mM extracellular potassium was not sensitive to verapamil or diltiazem at 10 μM. 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 μM 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.

LanguageEnglish
Pages1296-1303
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume252
Issue number3
Publication statusPublished - 1 Mar 1990
Externally publishedYes

Fingerprint

Chromaffin Cells
Phosphatidylinositols
Cyclic AMP
Prostaglandins
Norepinephrine
Alprostadil
Inositol Phosphates
Prostaglandins F
Bradykinin
Calcium
Calcium Channel Agonists
Diltiazem
Calcium Channel Blockers
Second Messenger Systems
Verapamil
Nicotine
Dinoprostone
Potassium
Hydrolysis
Down-Regulation

Cite this

@article{f69309ab49654d939c4f4d99c7470672,
title = "Role of phosphoinositide turnover and cyclic AMP accumulation in prostaglandin-stimulated noradrenaline release from cultured adrenal chromaffin cells",
abstract = "Prostaglandins (PGs) E1, E2 and F(2α) stimulated release of noradrenaline from chromaffin cells; the most potent was PGF(2α) with an EC50 of about 0.1 μM. 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 μM, but unlike release stimulated by 50 mM extracellular potassium was not sensitive to verapamil or diltiazem at 10 μM. 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 μM 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.",
author = "R. Plevin and Owen, {P. J.} and Marriott, {D. B.} and Jones, {J. A.} and Boarder, {M. R.}",
year = "1990",
month = "3",
day = "1",
language = "English",
volume = "252",
pages = "1296--1303",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "3",

}

Role of phosphoinositide turnover and cyclic AMP accumulation in prostaglandin-stimulated noradrenaline release from cultured adrenal chromaffin cells. / Plevin, R.; Owen, P. J.; Marriott, D. B.; Jones, J. A.; Boarder, M. R.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 252, No. 3, 01.03.1990, p. 1296-1303.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Role of phosphoinositide turnover and cyclic AMP accumulation in prostaglandin-stimulated noradrenaline release from cultured adrenal chromaffin cells

AU - Plevin, R.

AU - Owen, P. J.

AU - Marriott, D. B.

AU - Jones, J. A.

AU - Boarder, M. R.

PY - 1990/3/1

Y1 - 1990/3/1

N2 - Prostaglandins (PGs) E1, E2 and F(2α) stimulated release of noradrenaline from chromaffin cells; the most potent was PGF(2α) with an EC50 of about 0.1 μM. 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 μM, but unlike release stimulated by 50 mM extracellular potassium was not sensitive to verapamil or diltiazem at 10 μM. 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 μM 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.

AB - Prostaglandins (PGs) E1, E2 and F(2α) stimulated release of noradrenaline from chromaffin cells; the most potent was PGF(2α) with an EC50 of about 0.1 μM. 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 μM, but unlike release stimulated by 50 mM extracellular potassium was not sensitive to verapamil or diltiazem at 10 μM. 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 μM 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.

UR - http://www.scopus.com/inward/record.url?scp=0025257456&partnerID=8YFLogxK

UR - http://jpet.aspetjournals.org/content/252/3/1296

M3 - Article

VL - 252

SP - 1296

EP - 1303

JO - Journal of Pharmacology and Experimental Therapeutics

T2 - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 3

ER -