Saxena A K, Saksena A K, Vrat S, Tangri K K
Naunyn Schmiedebergs Arch Pharmacol. 1987 Jul;336(1):81-6. doi: 10.1007/BF00177755.
The effects of microinjection of opioid receptor agonist and antagonist into mesencephalic nucleus dorsalis raphe, were studied on mean arterial pressure and heart rate to elucidate the nature and role of these opioid receptors in cardiovascular regulation. Microinjection of morphine (5 micrograms and 10 micrograms) into nucleus dorsalis raphe elicited both inhibitory and excitatory cardiovascular responses respectively, while microinjection of opioid receptor antagonist, naloxone (10 micrograms) failed to produce any significant cardiovascular responses. However, local pretreatment with naloxone blocked both inhibitory and excitatory responses of graded doses of morphine. These opioid receptors seem to be localised in the neurons of the nucleus since microinjection of morphine into neural structures adjoining nucleus dorsalis raphe failed to induce any cardiovascular responses. Furthermore, the dose or morphine (2 micrograms) which was ineffective when microinjected into nucleus dorsalis raphe, produced inhibitory cardiovascular responses after pretreatment with LM5008, a 5-HT uptake blocker. Similarly, the excitatory cardiovascular responses of morphine microinjection were blocked by spinal cord transection (C1) and p-CPA, guanethidine and piperoxan pretreatments, while bilateral cervical vagotomy failed to do so. Thus, it is likely that the inhibitory cardiovascular responses of morphine are mediated directly through stimulation of opioid receptors present in the neurons of nucleus dorsalis raphe while the excitatory responses to higher dose of morphine, appear to be due to a release of noradrenaline which in turn modulates the activity of neurons by acting on alpha adrenoceptors.
将阿片受体激动剂和拮抗剂微量注射到中脑背侧缝际核,研究其对平均动脉压和心率的影响,以阐明这些阿片受体在心血管调节中的性质和作用。将吗啡(5微克和10微克)微量注射到背侧缝际核分别引起抑制性和兴奋性心血管反应,而微量注射阿片受体拮抗剂纳洛酮(10微克)未产生任何显著的心血管反应。然而,用纳洛酮进行局部预处理可阻断不同剂量吗啡的抑制性和兴奋性反应。这些阿片受体似乎定位于该核的神经元中,因为将吗啡微量注射到与背侧缝际核相邻的神经结构中未能诱导任何心血管反应。此外,当微量注射到背侧缝际核无效的吗啡剂量(2微克),在用5-羟色胺摄取阻滞剂LM5008预处理后产生抑制性心血管反应。同样,微量注射吗啡的兴奋性心血管反应被脊髓横断(C1)以及对氯苯丙氨酸、胍乙啶和哌罗克生预处理所阻断,而双侧颈迷走神经切断术则不能阻断。因此,吗啡的抑制性心血管反应可能是通过直接刺激背侧缝际核神经元中存在的阿片受体介导的,而对高剂量吗啡的兴奋性反应似乎是由于去甲肾上腺素的释放,而去甲肾上腺素又通过作用于α肾上腺素受体来调节神经元的活动。