PACAP-38 activates parasympathetic nerves in isolated, blood-perfused dog atria
PACAP-38 activates parasympathetic nerves in isolated, blood-perfused dog atria
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DOI：
10.1016/s0014-2999(96)00609-7
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发表时间：
1996-11-21
影响因子：
5
通讯作者：
Chiba, S
中科院分区：
文献类型：
--
作者：
Yonezawa, T;Furukawa, Y;Chiba, S
垂体腺苷酸环化酶激活多肽 (PACAP) 可激活 PACAP 和血管活性肠肽 (VIP) 受体。我们研究了 PACAP-38 对离体、血液灌注狗心脏制剂中窦率和心房收缩力的影响以及 PACAP-38 对副交感神经纤维的刺激。 PACAP-38 (3-1000 pmol) 引起正向和/或负向变时性反应，并且它剂量依赖性地增加心房和心室收缩力。与 VIP 不同，PACAP-38 的阳性心脏反应远低于去甲肾上腺素的阳性反应。阿托品抑制 PACAP-38 的负变时反应，并增强正变时和正性肌力反应。毒扁豆碱增强了 PACAP-38 和乙酰胆碱的负面心脏反应。此外，毒扁豆碱治疗后，河豚毒素还可阻断心脏对 PACAP-38 和心内副交感神经刺激的负面反应。普萘洛尔不会抑制阿托品治疗的心房中对 PACAP-38 的阳性心脏反应。 PACAP-(6-38)（1 和 3 nmol）是 PACAP-38 的拮抗剂，不影响对 100 pmol PACAP-38 的心脏反应。这些结果表明，(1) PACAP-38 直接增加窦率和心房收缩力，(2) PACAP-38 激活副交感神经并在狗心脏中引起负变时性和正性肌力反应。
A pituitary adenylate cyclase-activating polypeptide (PACAP) activates PACAP and vasoactive intestinal peptide (VIP) receptors. We investigated the effects of PACAP-38 on the sinus rate and atrial contractile force in isolated, blood-perfused dog heart preparations and the stimulation by PACAP-38 of the parasympathetic nerve fibers. PACAP-38 (3-1000 pmol) caused positive and/or negative chronotropic responses and it dose dependently increased atrial and ventricular contractile force. The positive cardiac responses to PACAP-38 unlike those to VIP were much less than the positive responses to norepinephrine. Atropine inhibited the negative chronotropic responses to PACAP-38 and augmented the positive chronotropic and inotropic responses. Physostigmine potentiated the negative cardiac responses to PACAP-38 and acetylcholine. After physostigmine treatment, additionally, tetrodotoxin blocked the negative cardiac responses to PACAP-38 and intracardiac parasympathetic nerve stimulation. Propranolol did not inhibit the positive cardiac responses to PACAP-38 in atropine-treated atria. PACAP-(6-38) (1 and 3 nmol), an antagonist of PACAP-38, did not affect the cardiac responses to 100 pmol of PACAP-38. These results suggest that (1) PACAP-38 directly increases sinus rate and atrial contractile force and (2) PACAP-38 activates parasympathetic nerves and causes negative chronotropic and inotropic responses in the dog heart.