Rady J J, Gorny J M, Fujimoto J M
Research Service, Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53295, USA.
Jpn J Pharmacol. 1998 Dec;78(4):443-54. doi: 10.1254/jjp.78.443.
CD-1 mice were treated intravenously with streptozotocin, 200 mg/kg, and tested 2 weeks later or treated with 60 mg/kg and tested 3 days later. Both treatments changed the tail flick response of heroin and 6-monoacetylmorphine (6 MAM) given intracerebroventricularly from a mu- to delta-opioid receptor-mediated action as determined by differential effects of opioid receptor antagonists. The response to morphine remained mu. Heroin and 6 MAM responses involved delta1 (inhibited by 7-benzylidenenaltrexone) and delta2 (inhibited by naltriben) receptors, respectively. These delta-agonist actions did not synergize with the mu-agonist action of morphine in the diabetic mice. The expected synergism between the delta agonist, [D-Pen2-D-Pen5]enkephalin (DPDPE), and morphine was not obtained in diabetic mice. Thus, diabetes disrupted the purported mu/delta-coupled response. In nondiabetic CD-1 mice, heroin and 6 MAM produced a different mu-receptor response (not inhibited by naloxonazine) from that of morphine (inhibited by naloxonazine). Also, these mu actions, unlike that of morphine, did not synergize with DPDPE. The unique receptor actions and changes produced by streptozotocin suggest that extrinsic in addition to genetic factors influence the opioid receptor selectivity of heroin and 6 MAM.
给CD - 1小鼠静脉注射200毫克/千克链脲佐菌素，2周后进行测试；或注射60毫克/千克，3天后进行测试。两种处理均改变了脑室内注射海洛因和6 - 单乙酰吗啡（6 MAM）的甩尾反应，从μ阿片受体介导的作用转变为由阿片受体拮抗剂的不同作用所确定的δ阿片受体介导的作用。对吗啡的反应仍为μ介导。海洛因和6 MAM的反应分别涉及δ1受体（被7 - 苄叉基纳曲酮抑制）和δ2受体（被纳曲苄抑制）。在糖尿病小鼠中，这些δ激动剂的作用与吗啡的μ激动剂作用不协同。在糖尿病小鼠中未获得预期的δ激动剂[D - Pen2 - D - Pen5]脑啡肽（DPDPE）与吗啡之间的协同作用。因此，糖尿病破坏了所谓的μ/δ偶联反应。在非糖尿病的CD - 1小鼠中，海洛因和6 MAM产生了与吗啡不同的μ受体反应（不被纳洛嗪抑制）。而且，这些μ作用与吗啡不同，不与DPDPE协同。链脲佐菌素产生的独特受体作用和变化表明，除了遗传因素外，外在因素也会影响海洛因和6 MAM的阿片受体选择性。
