N. Lepretre et al., ACTIVATION OF ALPHA-1A ADRENOCEPTORS MOBILIZES CALCIUM FROM THE INTRACELLULAR STORES IN MYOCYTES FROM RAT PORTAL-VEIN, The Journal of pharmacology and experimental therapeutics, 268(1), 1994, pp. 167-174
Intracellular free Ca++ concentration ([Ca++](i)) was monitored using
the fluorescence from the dye fura-2-acetoxymethylester in single myoc
ytes from rat portal vein. In the presence of oxodipine (a L-type Ca+ channel inhibitor), norepinephrine (10 mu M) evoked transient increas
es in [Ca++](i) which were related to release of Ca++ from intracellul
ar stores. The alpha-1 adrenoceptors mediating intracellular Ca++ rele
ase and inositol phosphate accumulation were identified by using subty
pe-selective agonists and antagonists. Pretreatment with chloroethylcl
onidine had little effect on the norepinephrine-induced increase in [C
a++](i) and inositol phosphate accumulation. In contrast, prazosin, di
methoxyphenoxyethyl)aminomethyl-1,4-benzodioxane and xyphenoxy)ethyl)-
amino)-propyl)benzeneacetonitrile fumarate produced a concentration-de
pendent inhibition of both intracellular Ca++ release and inositol pho
sphate accumulation. The rank of potency was prazosin > dimethoxypheno
xyethyl)aminomethyl-1,4-benzodioxane > pha-(3-((2-(2-methoxyphenoxy)et
hyl)-amino)-propyl) benzeneacetonitrile fumarate. Methoxamine was as e
ffective as norepinephrine but was less potent as shown by the rightwa
rd shift of the concentration-response curves. These results indicate
that myocytes from rat portal vein express alpha-1A adrenoceptors whos
e activation stimulates phosphoinositide turnover and release of Ga+from intracellular stores. The alpha-1A adrenoceptor stimulation of [C
a++](i) and subsequent activation of Ca++-activated Cl- current was in
sensitive to intracellular applications of pertussis toxin, but concen
tration-dependently blocked by intracellular dialysis with a pipette s
olution containing anti-alpha(q)/alpha(11) antibody (whole cell record
ing mode). These data suggest that a Gq/G11 quanine nucleotide-binding
protein is responsible for activation of a phosphatidylinositol-speci
fic phospholipase C leading to production of inositol 1,4,5-trisphosph
ate.