Studies on the characterization of the subtype(s) of muscarinic receptor involved in prostacyclin synthesis in rabbit cardiomyocytes

Manoj G. Tyagi, Hong Kan, Ying Ruan, Kafait Malik

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The present study was conducted to localize and characterize the subtype(s) of muscarinic receptor involved in prostacyclin (PGI2) production elicited by the cholinergic transmitter acetylcholine (ACh) in various cell types in the rabbit heart. ACh increased PGI2 synthesis measured as 6-keto- PGF1α, in cultured coronary endothelial cells and freshly dissociated ventricular myocytes in a dose dependent manner but not in cultured coronary smooth muscle cells of rabbit heart. McN-A-343, a partially selective M1 muscarinic ACh receptor (mAChR) agonist, did not alter 6-keto-PGF1α synthesis in these cell types. ACh induced 6-keto-PGF1α synthesis in coronary endothelial cells and ventricular myocytes was not altered by a low concentration (10-8 M) of pirenzipine, an M1 mAChR antagonist but was reduced by a higher concentration (10-6 M). In coronary endothelial cells ACh induced 6-keto-PGF1α production was reduced by hexahydro-sila-difendial (HHSiD), an M3 mAChR antagonist, and in ventricular myocytes by both 11- {2-[(di-ethylamino) methyl]-1-piperidinyl]acetyl-5,11-dihydro-6-H-pyrido- [2,3-b]-benzodiazepine-6 one} (AF-DX 116), an M2 receptor antagonist, and HHSiD. The decrease by ACh of isoproterenol stimulated cAMP accumulation was minimized by AF-DX 116 but not by HHSiD or pirenzipine. Pertussis toxin treatment minimized ACh induced decrease in isoproterenol stimulated rise in cAMP and ATP release, but not ACh induced 6-keto-PGF1α synthesis. These data suggest that ACh stimulates prostacyclin production in coronary endothelial cells via M3 mAChR and in ventricular myocytes M2 and M3 mAChR. Moreover, ACh induced decrease in cAMP, but not the increase in 6-keto-PGF1α production, is mediated by pertussis toxin sensitive Gαi proteins in these cells.

Original languageEnglish (US)
Pages (from-to)273-296
Number of pages24
JournalJournal of Receptor and Signal Transduction Research
Volume16
Issue number5-6
DOIs
StatePublished - Jan 1 1996

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Muscarinic Receptors
Epoprostenol
Cardiac Myocytes
Acetylcholine
Rabbits
Cholinergic Agents
Endothelial cells
Cholinergic Receptors
Muscle Cells
Endothelial Cells
Pertussis Toxin
Isoproterenol
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
Cholinergic Agonists
Benzodiazepines
Smooth Muscle Myocytes
Muscle
prostaglandin F1
Transmitters
Adenosine Triphosphate

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Studies on the characterization of the subtype(s) of muscarinic receptor involved in prostacyclin synthesis in rabbit cardiomyocytes. / Tyagi, Manoj G.; Kan, Hong; Ruan, Ying; Malik, Kafait.

In: Journal of Receptor and Signal Transduction Research, Vol. 16, No. 5-6, 01.01.1996, p. 273-296.

Research output: Contribution to journalArticle

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