Mg. Tyagi et al., STUDIES ON THE CHARACTERIZATION OF THE SUBTYPE(S) OF MUSCARINIC RECEPTOR INVOLVED IN PROSTACYCLIN SYNTHESIS IN RABBIT CARDIOMYOCYTES, Journal of receptor and signal transduction research, 16(5-6), 1996, pp. 273-296
The present study was conducted to localize and characterize the subty
pe(s) of muscarinic receptor involved in prostacyclin (PGI(2)) product
ion elicited by the cholinergic transmitter acetylcholine (ACh) in var
ious cell types in the rabbit heart. ACh increased PGI(2) synthesis me
asured as 6-keto-PGF1 alpha, in cultured coronary endothelial cells an
d 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 M(1) muscarinic ACh receptor (mAChR) agon
ist, did not alter 6-keto-PGF1 alpha synthesis in these cell types. AC
h induced 6-keto-PGF1 alpha synthesis in coronary endothelial cells an
d ventricular myocytes was not altered by a low concentration (10(-8)
M) of pirenzipine, an M(1) mAChR antagonist but was reduced by a highe
r concentration (10(-6) M). In coronary endothelial cells ACh induced
6-keto-PGF1 alpha production was reduced by hexahydro-situ-difendial (
HHSiD), an M(3) mAChR antagonist, and in ventricular myocytes by both
l-5,11-dihydro-6-H-pyrido-[2,3-b]-benzodiazepine-6 one} (AF-DX 116), a
n M(2) receptor antagonist, and HHSiD. The decrease by ACh of isoporte
renol stimulated cAMP accumulation was minimized by AF-DX 116 but not
by HHSiD or pirenzipine. Pertussis toxin treatment minimized ACh induc
ed decrease in isoproterenol stimulated rise in cAMP and ATP release,
but not ACh induced 6-keto-PGF1 alpha synthesis. These data suggest th
at ACh stimulates prostacyclin production in coronary endothelial cell
s via M(3) mAChR and in ventricular myocytes M(2) and M(3) mAChR. More
over, ACh induced decrease in cAMP, but not the increase in 6-keto-PGF
1 alpha production, is mediated by pertussis toxin sensitive G alpha i
proteins in these cells.