Houdi A A, Marson L, Davenport K E, Van Loon G R
Department of Medicine, University of Kentucky, Lexington 40536, USA.
Pharmacol Biochem Behav. 1996 Apr;53(4):927-33. doi: 10.1016/0091-3057(95)02139-6.
To elucidate further the role of mu-opioid receptors in mediating analgesia and cardiovascular function at rest and during stress, rats were pretreated ICV with either saline (5 microliters) or beta-funaltrexamine (beta-FNA, 5 nmol/5 microliters), a noncompetitive opioid receptor antagonist that inactivates irreversibly mu receptors, 2 days prior to [D-Ala2, N MePhe4, Gly5-ol]enkephalin (DAMPGO, 1 nmol, ICV) administration. Pretreatment with beta-FNA blocked DAMPGO-induced analgesia as measured by the tail-flick test. DAMPGO also produced an increase in blood pressure (BP), sympathoadrenal outflow, and a bradycardia. Pretreatment with beta-FNA converted the DAMPGO-induced bradycardia to a tachycardia, significantly reduced the DAMPGO-induced increase in epinephrine by 60%, and the norepinephrine response by 45%, and attenuated mildly the increase in BP due to DAMPGO. In saline-treated rats, restraint stress evoked an increase in HR, BP, and plasma catecholamines. Pretreatment with beta-FNA partially attenuated the increase in HR in response to stress. In the presence of DAMPGO, restraint stress resulted in a further bradycardia, which was significantly blocked by pretreatment with beta-FNA. Stress also produced increases in BP and plasma catecholamines, which were not prevented by pretreating rats with beta-FNA. These results indicate that beta-FNA may not have inactivated all the receptors accessible to DAMPGO which control BP, or alternatively, beta-FNA may selectively inactivate a subtype of mu receptors. In addition, brain mu opioid receptors appear to be significantly involved in mediating supraspinal analgesia and regulating parasympathetic outflow to the heart and sympathoadrenal release of catecholamines.
为了进一步阐明μ-阿片受体在静息和应激状态下介导镇痛及心血管功能中的作用，在给予[D-丙氨酸2，N-甲基苯丙氨酸4，甘氨酸5-醇]脑啡肽（DAMPGO，1 nmol，脑室内注射）前2天，给大鼠脑室内预先注射生理盐水（5微升）或β-氟纳曲酮（β-FNA，5 nmol/5微升），β-氟纳曲酮是一种不可逆地使μ受体失活的非竞争性阿片受体拮抗剂。通过甩尾试验测量，β-FNA预处理可阻断DAMPGO诱导的镇痛作用。DAMPGO还可使血压（BP）升高、交感肾上腺系统传出增加以及出现心动过缓。β-FNA预处理使DAMPGO诱导的心动过缓转变为心动过速，显著降低了DAMPGO诱导的肾上腺素增加60%，去甲肾上腺素反应降低45%，并轻度减弱了DAMPGO引起的血压升高。在生理盐水处理的大鼠中，束缚应激可引起心率（HR）、血压和血浆儿茶酚胺升高。β-FNA预处理可部分减弱对应激的心率升高反应。在存在DAMPGO的情况下，束缚应激导致进一步的心动过缓，而β-FNA预处理可显著阻断该反应。应激还可使血压和血浆儿茶酚胺升高，β-FNA预处理不能阻止这种升高。这些结果表明，β-FNA可能并未使DAMPGO可作用的所有控制血压的受体失活，或者β-FNA可能选择性地使μ受体的一个亚型失活。此外，脑内μ阿片受体似乎在介导脊髓上镇痛以及调节心脏的副交感神经传出和交感肾上腺系统儿茶酚胺释放中起重要作用。
