Takayama S, Furukawa Y, Ren L M, Inoue Y, Sawaki S, Chiba S
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Eur J Pharmacol. 1993 Feb 16;231(3):315-21. doi: 10.1016/0014-2999(93)90105-q.
We investigated the chronotropic and inotropic responses to BRL 37344 (a beta 3-adrenoceptor agonist) and isoproterenol in isolated, blood-perfused dog atria. BRL 37344 (0.1-30 nmol) or isoproterenol (0.001-0.3 nmol) increased the sinus rate and contractile force dose dependently. BRL 37344 was 290 times less potent than isoproterenol to increase sinus rate and 140 times less potent to increase atrial force. Both propranolol and bisoprolol similarly inhibited the positive chronotropic and inotropic responses to BRL 37344 and isoproterenol dose dependently. ICI 118,551 (0.1 and 1 nmol) did not significantly affect the positive cardiac responses to BRL 37344 or isoproterenol. Neither imipramine nor tetrodotoxin significantly affected the positive cardiac responses to BRL 37344. These results suggest that the positive chronotropic and inotropic responses to BRL 37344 are mediated mainly by beta 1-adrenoceptors in the dog heart. It is unlikely that beta 3-adrenoceptors, as previously reported in adipose tissue or gastrointestinal smooth muscle, mediate chronotropic and inotropic responses in the normal dog heart.
我们研究了在离体、血液灌注的犬心房中，BRL 37344（一种β3肾上腺素能受体激动剂）和异丙肾上腺素对变时性和变力性的反应。BRL 37344（0.1 - 30 nmol）或异丙肾上腺素（0.001 - 0.3 nmol）剂量依赖性地增加窦性心率和收缩力。BRL 37344增加窦性心率的效力比异丙肾上腺素低290倍，增加心房力的效力低140倍。普萘洛尔和比索洛尔均同样地剂量依赖性抑制对BRL 37344和异丙肾上腺素的正性变时性和变力性反应。ICI 118,551（0.1和1 nmol）对BRL 37344或异丙肾上腺素引起的心脏正性反应无显著影响。丙咪嗪和河豚毒素对BRL 37344引起的心脏正性反应均无显著影响。这些结果表明，犬心脏中对BRL 37344的正性变时性和变力性反应主要由β1肾上腺素能受体介导。在正常犬心脏中，β3肾上腺素能受体介导变时性和变力性反应的可能性不大，而β3肾上腺素能受体在脂肪组织或胃肠道平滑肌中曾有过报道。
