Alpha 1-adrenoceptor subtypes mediating the regulation and modulation of Ca2+ sensitization in rabbit thoracic aorta.
Norepinephrine (10 microM), methoxamine (100 microM) and clonidine (100 microM) with guanosine 5'-triphosphate (GTP, 50 microM) or guanosine 5'-O-(3-thiotriphosphate) (GTP gamma-S, 10 microM) all significantly enhanced the contraction induced by 0.3 microM Ca2+ (pCa6.5) in beta-escin-skinned smooth muscle of rabbit thoracic aorta. The enhancement of Ca2+ contraction produced by norepinephrine was greater than that produced by methoxamine or clonidine. In beta-escin-skinned strips of chloroethylclonidine-pretreated smooth muscle, the enhancement of Ca2+ contraction produced by norepinephrine was significantly decreased, whereas the amplitude was the same as that produced by methoxamine or clonidine; this enhancement was inhibited by the selective alpha 1A-adrenoceptor antagonist WB 4101 (100 nM). The enhancement of Ca2+ contraction produced by methoxamine and clonidine was not affected by chloroethylclonidine pretreatment. The effects of methoxamine, clonidine and norepinephrine in the chloroethylclonidine-pretreated tissue were all inhibited by guanosine 5'-O-(2-thiodiphosphate) (GDP beta-S, 1 mM) and 1-(5-isoquinolinylsulfonyl)-methylpiperazine (H-7, 20 microM). Furthermore, the phosphorylation of myosin light chain produced by norepinephrine was greater than that produced by clonidine. These results suggest that both alpha 1-adrenoceptor subtypes (alpha 1A and alpha 1B) increase the Ca2+ sensitivity of contractile elements, and that the Ca2+ sensitization produced by alpha 1A-subtype receptors is mediated through G-protein and protein kinase C, and plays an important role in contraction of smooth muscle of rabbit thoracic aorta.
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Ca2+ GTP gamma-S Ca2+ methoxamine Ca2+ norepinephrine methoxamine clonidine chloroethylclonidine Ca2+ Norepinephrine clonidine norepinephrine methoxamine clonidine WB 4101 Ca2+ guanosine 5'-triphosphate methoxamine clonidine chloroethylclonidine chloroethylclonidine methoxamine clonidine norepinephrine Ca2+ myosin light chain alpha 1-adrenoceptor subtypes (alpha 1A and alpha 1B alpha 1A-subtype receptors G-protein protein kinase C alpha 1A-adrenoceptor guanosine 5'-O-(2-thiodiphosphate) Alpha 1-adrenoceptor GDP beta-S 1-(5-isoquinolinylsulfonyl)-methylpiperazine norepinephrine clonidine guanosine 5'-O-(3-thiotriphosphate) Ca2+