Smith D J, Perrotti J M, Crisp T, Cabral M E, Long J T, Scalzitti J M
Department of Anesthesiology, West Virginia University Medical Center, Morgantown 26506.
Eur J Pharmacol. 1988 Oct 26;156(1):47-54. doi: 10.1016/0014-2999(88)90145-8.
Opiate agonists exhibiting selectivity for mu, kappa, sigma, and delta opiate receptors were microinjected into the periaqueductal gray region (PAG) of the brain of rats to determine the receptor subtype(s) associated with the initiation of descending pain inhibition. The spinally organized, heat nociceptive tail-flick reflex was used to detect analgesia. Only morphine (mu) and [D-Ala2,D-Leu5]enkephalin (DADLE) (delta greater than mu) produced analgesia. However, both drugs appeared to be acting through the mu (morphine) receptor, since: (1) the action of DADLE was not inhibited by delta receptor antagonists, (2) a more highly selective delta agonist [D-Pen2,D-Pen5]enkephalin was ineffective and (3) agonists selective at other non-mu receptor sites (ethylketocyclazocine and U50,488H for kappa; n-allylnormetazocine for sigma) were also ineffective. It appeared that DADLE might be acting as a partial agonist at the morphine receptor in the PAG. The peptide was an agonist with low efficacy, and when a maximally effective dose of the peptide was administered simultaneously with morphine antagonism was observed. Ethylketocyclazocine and n-allylnormetazocine were also found to antagonize morphine, an observation that is consistent with the suggestion that they may act as mu receptor antagonists in addition to their agonistic action at kappa and sigma receptors, respectively. Thus, mu receptors appear to be responsible for the spinopetal analgesia from the PAG of the rat.
将对μ、κ、σ和δ阿片受体具有选择性的阿片类激动剂微量注射到大鼠脑导水管周围灰质区域（PAG），以确定与下行性疼痛抑制起始相关的受体亚型。利用脊髓组织的热伤害性甩尾反射来检测镇痛效果。只有吗啡（μ）和[D - Ala2，D - Leu5]脑啡肽（DADLE）（δ大于μ）产生了镇痛作用。然而，这两种药物似乎都是通过μ（吗啡）受体起作用的，因为：（1）DADLE的作用不受δ受体拮抗剂的抑制；（2）一种选择性更高的δ激动剂[D - Pen2，D - Pen5]脑啡肽无效；（3）对其他非μ受体位点具有选择性的激动剂（κ受体的乙基酮环唑新和U50,488H；σ受体的烯丙基去甲左啡诺）也无效。似乎DADLE可能在PAG中作为吗啡受体的部分激动剂起作用。该肽是一种低效激动剂，当与吗啡同时给予最大有效剂量的该肽时，观察到了拮抗作用。还发现乙基酮环唑新和烯丙基去甲左啡诺也拮抗吗啡，这一观察结果与它们除了分别在κ和σ受体上具有激动作用外，还可能作为μ受体拮抗剂的观点一致。因此，μ受体似乎是大鼠PAG产生向心性镇痛的原因。
