Effects of specific alpha-adrenoceptive agents on extraneuronal uptake (uptake2) of isoproterenol in perfused rat heart.
Effects of specific alpha-adrenoceptive agents (alpha 1-agonist, alpha 1-antagonist, alpha 2-agonist and alpha 2-antagonist) on the extraneuronal accumulation of 3H-isoproterenol in the perfused rat heart were examined. The extraneuronal accumulation of 3H-isoproterenol in the hearts perfused with 3H-isoproterenol (10(-6)M) under COMT inhibition by tropolone (10(-4)M) was about 6 times higher than that of intact COMT. The increase in the accumulation by COMT inhibition was regarded as 100% and the effects of specific alpha-adrenoceptive agents on the accumulation was evaluated. alpha 1-agonists, methoxamine and phenylephrine, did not affect the accumulation. alpha 1-antagonists, prazosin, bunazosin and YM-12617, significantly decreased the accumulation of 3H-isoproterenol and these IC50 values were 2 x 10(-6)M, 3.5 x 10(-6)M and 2.3 x 10(-5)M, respectively. alpha 2-agonists, clonidine and guanabenz, significantly reduced the accumulation and these IC50 values were 3.4 x 10(-5)M and 2.9 x 10(-7)M, respectively. The alpha 2-antagonist, yohimbine, did not affect the accumulation. The present experiments clearly demonstrated that the tested alpha 1-antagonists and alpha 2-agonists inhibited uptake2 in rat heart but the tested alpha 1-agonists and an alpha 2-antagonist did not inhibit it.
Akimoto
Y
Y
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
Sono
K
K
Kurahashi
K
K
Fujiwara
M
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D006143:Guanabenz / Q000494:pharmacology; D007545:Isoproterenol / Q000378:metabolism*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology; D014334:Tropolone / Q000494:pharmacology; D000096926:Benzenesulfonamides
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D003000:Clonidine; D006143:Guanabenz; D007545:Isoproterenol; D008729:Methoxamine; D010656:Phenylephrine; D011224:Prazosin; D011799:Quinazolines; D013449:Sulfonamides; D014334:Tropolone; C044648:YM 12617; D000096926:Benzenesulfonamides; C018176:bunazosin