Arreola J, Dirksen R T, Perez-Cornejo P, Piech K M, Sheu S S
Department of Dental Research, University of Rochester School of Medicine and Dentistry, NY 14642.
Eur J Pharmacol. 1994 Dec 27;271(2-3):309-17. doi: 10.1016/0014-2999(94)90788-9.
The effects of alpha 1-adrenoceptor and muscarinic acetylcholine receptor stimulation on action potential and tension were studied in guinea pig papillary muscles obtained from both right and left ventricles. Stimulation of muscarinic acetylcholine receptors with carbachol produced a reduction of the action potential duration and a positive inotropic effect in papillary muscles from both ventricles. Both effects were concentration dependent and atropine sensitive. However, differential responsiveness was found upon alpha 1-adrenoceptor activation in muscles obtained from left and right ventricles. In right side papillary muscles, the alpha 1-adrenoceptor agonist, methoxamine, decreased the action potential duration and produced a positive inotropic effect. In contrast, methoxamine decreased the action potential duration but failed to produce a positive inotropic effect in left side papillary muscles. All methoxamine effects were antagonized by prazosin. Responses to maximum concentration of carbachol and methoxamine on the action potential duration and contractility were additive in right side papillary muscles. Phorbol 12,13-dibutyrate (PDB), a direct protein kinase C activator, also decreased the action potential duration in a manner that was additive to both carbachol and methoxamine. However, PDB reversed the positive inotropic effect of carbachol and methoxamine. The methoxamine-induced shortening of the action potential duration was prevented by pretreatment with indomethacin and nordihydroguaiaretic acid, blockers of arachidonic acid metabolism, but not by the protein kinase C antagonist, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7).(ABSTRACT TRUNCATED AT 250 WORDS)
研究了α1-肾上腺素能受体和毒蕈碱型乙酰胆碱受体刺激对从豚鼠左右心室获取的乳头肌动作电位和张力的影响。用卡巴胆碱刺激毒蕈碱型乙酰胆碱受体可使两个心室乳头肌的动作电位时程缩短并产生正性肌力作用。这两种作用均呈浓度依赖性且对阿托品敏感。然而，在左右心室获取的肌肉中，α1-肾上腺素能受体激活时发现有不同的反应性。在右侧乳头肌中，α1-肾上腺素能受体激动剂甲氧明可缩短动作电位时程并产生正性肌力作用。相比之下，甲氧明可缩短左侧乳头肌的动作电位时程，但未产生正性肌力作用。所有甲氧明的作用均被哌唑嗪拮抗。右侧乳头肌对卡巴胆碱和甲氧明最大浓度刺激的动作电位时程和收缩性反应具有相加性。佛波醇12,13-二丁酸酯（PDB），一种直接的蛋白激酶C激活剂，也以与卡巴胆碱和甲氧明相加的方式缩短动作电位时程。然而，PDB可逆转卡巴胆碱和甲氧明的正性肌力作用。甲氧明诱导的动作电位时程缩短可被花生四烯酸代谢阻滞剂吲哚美辛和去甲二氢愈创木酸预处理所阻止，但不能被蛋白激酶C拮抗剂1-(5-异喹啉磺酰基)-2-甲基哌嗪（H-7）阻止。（摘要截短至250字）
