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.
Satoh
M
M
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Kojima
C
C
Kokubu
N
N
Takayanagi
I
I
D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009218:Myosins / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011817:Rabbits; D018341:Receptors, Adrenergic, alpha-2 / Q000145:classification* / Q000187:drug effects / Q000502:physiology*
D018341:Receptors, Adrenergic, alpha-2; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D009218:Myosins; D002118:Calcium