Existence of two components in the tonic contraction of rat aorta mediated by alpha 1-adrenoceptor activation.
1. The mechanisms involved in the contraction of rat aorta induced by the activation of alpha 1-adrenoceptors were studied. Phenylephrine induced a phasic contraction in the aorta incubated in Ca2(+)-free medium containing 0.5 mM EGTA. Subsequent addition of Ca2+ induced a tonic contraction, which exhibited a stepwise development, an initial phase lasting 3 to 6 min (tonic-I) followed by a superimposing second phase (tonic-II). 2. 2-Nitro-4-carboxyphenyl-N,N-diphenylcarbamate, which has been reported to inhibit phosphatidylinositol turnover, and H-7, a protein kinase C inhibitor, inhibited the tonic-I phase more effectively than the tonic-II phase. On the other hand, the tonic-II phase was more sensitive to nifedipine and cromakalim. 3. The rate of 45Ca2+ influx during the tonic-I phase in phenylephrine-treated muscles was not different from that in untreated muscles, while that during the tonic-II phase was significantly greater. Nifedipine inhibited the increased 45Ca2+ influx during the tonic-II phase, whereas H-7 did not affect the uptake during either phase. 4. These results suggest that the tonic contraction of rat aorta following alpha 1-adrenoceptor activation involves two different mechanism: one is directly related to consequences of the polyphosphoinositide cascade, probably to protein kinase C, and the other dependent on Ca2+ influx through nifedipine-sensitive Ca2+ channels.
Department of Veterinary Pharmacology, Faculty of Agriculture, Miyazaki University, Japan.
K
K
Nishimura
M
M
Ota
K
K
Ito
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002132:Calcium Radioisotopes; D002219:Carbamates / Q000494:pharmacology; D019806:Cromakalim; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D048448:Phenylcarbamates; D010656:Phenylephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats
D000316:Adrenergic alpha-Agonists; D001578:Benzopyrans; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D002219:Carbamates; D007546:Isoquinolines; D048448:Phenylcarbamates; D010716:Phosphatidylinositols; D010879:Piperazines; D011480:Protease Inhibitors; D011758:Pyrroles; D019806:Cromakalim; C025508:2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate; D010656:Phenylephrine; D007811:Lanthanum; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D009543:Nifedipine; D002118:Calcium