Werz M A, Grega D S, MacDonald R L
Department of Neurology, University of Michigan, Ann Arbor.
J Pharmacol Exp Ther. 1987 Oct;243(1):258-63.
The effects of selective mu, delta and kappa opioid agonists and antagonists were studied on somatic calcium-dependent action potentials recorded from mouse dorsal root ganglion (DRG) neurons grown in dissociated cell culture. The mu selective agonist, PL 017, and the delta selective agonist, [D-Pen2, L-Pen5] enkephalin (DPLPE), reduced action potential duration of a subpopulation (21/56) of DRG neurons. Leucine-enkephalin reduced action potential duration of all neurons sensitive to PL 017 or DPLPE, whereas 85% of neurons responding to leucine-enkephalin responded to either PL 017 or DPLPE. Only 15% of neurons responded to both PL 017 and DPLPE. There was no significant difference in the response to PL 017 or DPLPE when compared to leucine-enkephalin. In another experiment, the kappa selective agonist dynorphin A (DYN A), PL 017 and DPLPE reduced action potential duration of a subpopulation (15/67) of DRG neurons. There was a heterogeneous response among neurons to PL 017, DPLPE and DYN A inasmuch as 21.4% of neurons responded to all three agonists, 35.7% responded to PL 017 and DYN A, 35.7% responded only to PL 017 and 7.1% responded only to DYN A. Responses to the mu selective agonist PL 017 were antagonized by the reversible opioid antagonist naloxone and the selective mu antagonist SMS 201-995 in a concentration-dependent fashion. Responses to PL 017 were not altered by the selective delta antagonist ICI 174864. Responses to PL 017 were reduced by the irreversible, selective mu antagonists beta-funaltrexamine and naloxonazine in a concentration-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了选择性μ、δ和κ阿片受体激动剂及拮抗剂对从小鼠背根神经节(DRG)神经元分离细胞培养物中记录的体细胞钙依赖性动作电位的影响。μ选择性激动剂PL 017和δ选择性激动剂[D- Pen2,L- Pen5]脑啡肽(DPLPE)可缩短DRG神经元亚群(21/56)的动作电位持续时间。亮氨酸脑啡肽可缩短所有对PL 017或DPLPE敏感的神经元的动作电位持续时间,而对亮氨酸脑啡肽有反应的神经元中,85%对PL 017或DPLPE有反应。只有15%的神经元对PL 017和DPLPE均有反应。与亮氨酸脑啡肽相比,对PL 017或DPLPE的反应无显著差异。在另一项实验中,κ选择性激动剂强啡肽A(DYN A)、PL 017和DPLPE可缩短DRG神经元亚群(15/67)的动作电位持续时间。神经元对PL 017、DPLPE和DYN A的反应存在异质性,因为21.4%的神经元对所有三种激动剂均有反应,35.7%对PL 017和DYN A有反应,35.7%仅对PL 017有反应,7.1%仅对DYN A有反应。对μ选择性激动剂PL 017的反应可被可逆性阿片受体拮抗剂纳洛酮和选择性μ拮抗剂SMS 201-995以浓度依赖性方式拮抗。对PL 017的反应不受选择性δ拮抗剂ICI 174864的影响。对PL 017的反应可被不可逆性、选择性μ拮抗剂β-芬太尼丁和纳洛嗪以浓度依赖性方式降低。(摘要截短于250字)