TY - JOUR
T1 - Ca2+ channel blockers distinguish between G protein-coupled pharmacomechanical Ca2+ release and Ca2+ sensitization
AU - Kobayashi, S.
AU - Gong, M. C.
AU - Somlyo, A. V.
AU - Somlyo, A. P.
PY - 1991
Y1 - 1991
N2 - The effects of Ca2+ channel blockers on two modes of G protein-mediated pharmacomechanical coupling, Ca2+ release and modulation of Ca2+ sensitivity of the contractile apparatus, were investigated. Smooth muscles were permeabilized with Staphylococcal α-toxin or with β-escin to avoid effects due to block of sarcolemmal Ca2+ channels, while retaining receptor/G protein coupling. In permeabilized portal vein smooth muscle, verapamil and nifedipine inhibited Ca2+ release induced by an α1-adrenergic agonist (phenylephrine) and by guanosine 5'-O-(3-thiotriphosphate) (GTPγS), but not that induced by inositol 1,4,5-trisphosphate (InsP3). These Ca2+ channel blockers also did not block the phenylephrine- or GTPγS-induced force development at constant cytoplasmic Ca2+ (''Ca2+ sensitization''). An α1-blocker (prazosin) inhibited both the Ca2+-releasing and Ca2+-sensitizing effects of phenylephrine, but not those of GTPγS, nor did it block InsP3-induced Ca2+ release. We conclude that Ca2+ channel blockers selectively uncouple the Ca2+-releasing, but not the Ca2+-sensitizing, component of pharmacomechanical coupling. These findings raise the possibility that pharmacomechanical Ca2+ release may be modulated by dihydropyridine binding proteins at the level of G proteins/phospholipase C and also indicate a divergence of the Ca2+-releasing and Ca2+-sensitizing effects at some step prior to phospholipase C.
AB - The effects of Ca2+ channel blockers on two modes of G protein-mediated pharmacomechanical coupling, Ca2+ release and modulation of Ca2+ sensitivity of the contractile apparatus, were investigated. Smooth muscles were permeabilized with Staphylococcal α-toxin or with β-escin to avoid effects due to block of sarcolemmal Ca2+ channels, while retaining receptor/G protein coupling. In permeabilized portal vein smooth muscle, verapamil and nifedipine inhibited Ca2+ release induced by an α1-adrenergic agonist (phenylephrine) and by guanosine 5'-O-(3-thiotriphosphate) (GTPγS), but not that induced by inositol 1,4,5-trisphosphate (InsP3). These Ca2+ channel blockers also did not block the phenylephrine- or GTPγS-induced force development at constant cytoplasmic Ca2+ (''Ca2+ sensitization''). An α1-blocker (prazosin) inhibited both the Ca2+-releasing and Ca2+-sensitizing effects of phenylephrine, but not those of GTPγS, nor did it block InsP3-induced Ca2+ release. We conclude that Ca2+ channel blockers selectively uncouple the Ca2+-releasing, but not the Ca2+-sensitizing, component of pharmacomechanical coupling. These findings raise the possibility that pharmacomechanical Ca2+ release may be modulated by dihydropyridine binding proteins at the level of G proteins/phospholipase C and also indicate a divergence of the Ca2+-releasing and Ca2+-sensitizing effects at some step prior to phospholipase C.
KW - Guanosine 5'-triphosphate-binding protein
KW - Sarcoplasmic reticulum
KW - Signal transduction
KW - Smooth muscle
KW - Verapamil
KW - α-Toxin
KW - β-Escin
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U2 - 10.1152/ajpcell.1991.260.2.c364
DO - 10.1152/ajpcell.1991.260.2.c364
M3 - Article
C2 - 1899969
AN - SCOPUS:0026112219
SN - 0363-6143
VL - 260
SP - C364-C370
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 2 29-2
ER -