Prostacyclin synthesis elicited by cholinergic agonists is linked to activation of M2α and M2β muscarinic receptors in the rabbit aorta

N. Jaiswal, Kafait Malik

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

This study was conducted to investigate the subtypes of muscarinic receptors involved in the action of cholinergic agents on prostacyclin synthesis in the rabbit aorta. Prostacyclin production measured as 6-keto-PGF was assessed after exposing the aortic rings to different cholinergic agents. Acetylcholine (ACh) (M1 and M2 agonist) (1-10 μM) and arecaidine proparagyl ester (APE) (M2 selective agonist) (1-10 μM) enhanced 6-keto-PGF output in a concentration-dependent manner. A selective M1 receptor agonist, McN-A-343, at 1 μM-1 mM did not alter 6-keto-PGF output. ACH- and APE induced increases in 6-keto-PGF output were attenuated by the M1 M2 antagonist atropine (0.1 μM), M antagonist (AF-DX 116), (0.1-1.0 μM), and by selective M antagonist, hexahydro-sila-difendiol (HHSiD) (0.1-10 μM), but not by the M1 antagonist pirenzepine (1.0 μM). 6-Keto-PGF output elicited by ACh- or APE was not altered by the adrenergic receptor antagonist phentolamine and propranolol or by the nicotinic receptor blocker hexamethonium. Similarly, the arachidonic acid- or norepinephrine induced 6-keto-PGF accumulation was not altered by these muscarinic receptor antagonists. Indomethacin, a cyclooxygenase inhibitor, prevented arachidonic acid, ACh- or APE induced 6-keto-PGF output. Removal of the endothelium abolished the production of 6-keto-PGF elicited by ACH, APE, bradykinin, and calcium ionophore A 23187, but not that induced by angiotensin II, K+ or norepinephrine. These data suggests that vascular prostaglandin generation elicited by cholinergic agonists is mediated via activation of M and M but not M1 muscarinic receptors, which are most likely located on the endothelium.

Original languageEnglish (US)
Pages (from-to)267-280
Number of pages14
JournalProstaglandins
Volume39
Issue number3
DOIs
StatePublished - Jan 1 1990

Fingerprint

Muscarinic M2 Receptors
Cholinergic Agonists
Epoprostenol
Aorta
Chemical activation
Rabbits
Acetylcholine
Muscarinic Receptors
Arachidonic Acid
Cholinergic Agents
Endothelium
Norepinephrine
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
Muscarinic M1 Receptors
Pirenzepine
Hexamethonium
Muscarinic Antagonists
Adrenergic Antagonists
Cyclooxygenase Inhibitors
Calcium Ionophores

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology

Cite this

Prostacyclin synthesis elicited by cholinergic agonists is linked to activation of M2α and M2β muscarinic receptors in the rabbit aorta. / Jaiswal, N.; Malik, Kafait.

In: Prostaglandins, Vol. 39, No. 3, 01.01.1990, p. 267-280.

Research output: Contribution to journalArticle

@article{bddba9af73e642beab7c67be9201de69,
title = "Prostacyclin synthesis elicited by cholinergic agonists is linked to activation of M2α and M2β muscarinic receptors in the rabbit aorta",
abstract = "This study was conducted to investigate the subtypes of muscarinic receptors involved in the action of cholinergic agents on prostacyclin synthesis in the rabbit aorta. Prostacyclin production measured as 6-keto-PGF1α was assessed after exposing the aortic rings to different cholinergic agents. Acetylcholine (ACh) (M1 and M2 agonist) (1-10 μM) and arecaidine proparagyl ester (APE) (M2 selective agonist) (1-10 μM) enhanced 6-keto-PGF1α output in a concentration-dependent manner. A selective M1 receptor agonist, McN-A-343, at 1 μM-1 mM did not alter 6-keto-PGF1α output. ACH- and APE induced increases in 6-keto-PGF1α output were attenuated by the M1 M2 antagonist atropine (0.1 μM), M2α antagonist (AF-DX 116), (0.1-1.0 μM), and by selective M2β antagonist, hexahydro-sila-difendiol (HHSiD) (0.1-10 μM), but not by the M1 antagonist pirenzepine (1.0 μM). 6-Keto-PGF1α output elicited by ACh- or APE was not altered by the adrenergic receptor antagonist phentolamine and propranolol or by the nicotinic receptor blocker hexamethonium. Similarly, the arachidonic acid- or norepinephrine induced 6-keto-PGF1α accumulation was not altered by these muscarinic receptor antagonists. Indomethacin, a cyclooxygenase inhibitor, prevented arachidonic acid, ACh- or APE induced 6-keto-PGF1α output. Removal of the endothelium abolished the production of 6-keto-PGF1α elicited by ACH, APE, bradykinin, and calcium ionophore A 23187, but not that induced by angiotensin II, K+ or norepinephrine. These data suggests that vascular prostaglandin generation elicited by cholinergic agonists is mediated via activation of M2α and M2β but not M1 muscarinic receptors, which are most likely located on the endothelium.",
author = "N. Jaiswal and Kafait Malik",
year = "1990",
month = "1",
day = "1",
doi = "10.1016/0090-6980(90)90046-X",
language = "English (US)",
volume = "39",
pages = "267--280",
journal = "Prostaglandins",
issn = "0090-6980",
publisher = "Elsevier BV",
number = "3",

}

TY - JOUR

T1 - Prostacyclin synthesis elicited by cholinergic agonists is linked to activation of M2α and M2β muscarinic receptors in the rabbit aorta

AU - Jaiswal, N.

AU - Malik, Kafait

PY - 1990/1/1

Y1 - 1990/1/1

N2 - This study was conducted to investigate the subtypes of muscarinic receptors involved in the action of cholinergic agents on prostacyclin synthesis in the rabbit aorta. Prostacyclin production measured as 6-keto-PGF1α was assessed after exposing the aortic rings to different cholinergic agents. Acetylcholine (ACh) (M1 and M2 agonist) (1-10 μM) and arecaidine proparagyl ester (APE) (M2 selective agonist) (1-10 μM) enhanced 6-keto-PGF1α output in a concentration-dependent manner. A selective M1 receptor agonist, McN-A-343, at 1 μM-1 mM did not alter 6-keto-PGF1α output. ACH- and APE induced increases in 6-keto-PGF1α output were attenuated by the M1 M2 antagonist atropine (0.1 μM), M2α antagonist (AF-DX 116), (0.1-1.0 μM), and by selective M2β antagonist, hexahydro-sila-difendiol (HHSiD) (0.1-10 μM), but not by the M1 antagonist pirenzepine (1.0 μM). 6-Keto-PGF1α output elicited by ACh- or APE was not altered by the adrenergic receptor antagonist phentolamine and propranolol or by the nicotinic receptor blocker hexamethonium. Similarly, the arachidonic acid- or norepinephrine induced 6-keto-PGF1α accumulation was not altered by these muscarinic receptor antagonists. Indomethacin, a cyclooxygenase inhibitor, prevented arachidonic acid, ACh- or APE induced 6-keto-PGF1α output. Removal of the endothelium abolished the production of 6-keto-PGF1α elicited by ACH, APE, bradykinin, and calcium ionophore A 23187, but not that induced by angiotensin II, K+ or norepinephrine. These data suggests that vascular prostaglandin generation elicited by cholinergic agonists is mediated via activation of M2α and M2β but not M1 muscarinic receptors, which are most likely located on the endothelium.

AB - This study was conducted to investigate the subtypes of muscarinic receptors involved in the action of cholinergic agents on prostacyclin synthesis in the rabbit aorta. Prostacyclin production measured as 6-keto-PGF1α was assessed after exposing the aortic rings to different cholinergic agents. Acetylcholine (ACh) (M1 and M2 agonist) (1-10 μM) and arecaidine proparagyl ester (APE) (M2 selective agonist) (1-10 μM) enhanced 6-keto-PGF1α output in a concentration-dependent manner. A selective M1 receptor agonist, McN-A-343, at 1 μM-1 mM did not alter 6-keto-PGF1α output. ACH- and APE induced increases in 6-keto-PGF1α output were attenuated by the M1 M2 antagonist atropine (0.1 μM), M2α antagonist (AF-DX 116), (0.1-1.0 μM), and by selective M2β antagonist, hexahydro-sila-difendiol (HHSiD) (0.1-10 μM), but not by the M1 antagonist pirenzepine (1.0 μM). 6-Keto-PGF1α output elicited by ACh- or APE was not altered by the adrenergic receptor antagonist phentolamine and propranolol or by the nicotinic receptor blocker hexamethonium. Similarly, the arachidonic acid- or norepinephrine induced 6-keto-PGF1α accumulation was not altered by these muscarinic receptor antagonists. Indomethacin, a cyclooxygenase inhibitor, prevented arachidonic acid, ACh- or APE induced 6-keto-PGF1α output. Removal of the endothelium abolished the production of 6-keto-PGF1α elicited by ACH, APE, bradykinin, and calcium ionophore A 23187, but not that induced by angiotensin II, K+ or norepinephrine. These data suggests that vascular prostaglandin generation elicited by cholinergic agonists is mediated via activation of M2α and M2β but not M1 muscarinic receptors, which are most likely located on the endothelium.

UR - http://www.scopus.com/inward/record.url?scp=0025210366&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025210366&partnerID=8YFLogxK

U2 - 10.1016/0090-6980(90)90046-X

DO - 10.1016/0090-6980(90)90046-X

M3 - Article

VL - 39

SP - 267

EP - 280

JO - Prostaglandins

JF - Prostaglandins

SN - 0090-6980

IS - 3

ER -