Maeda Y, Yamada K, Hasegawa T, Nabeshima T
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Eur J Pharmacol. 1995 Mar 6;275(2):163-70. doi: 10.1016/0014-2999(94)00764-x.
To elucidate the mechanism of antinociceptive effects of calcitonin, we investigated whether receptor antagonists for various neurotransmitter receptors alter the inhibitory effect of calcitonin on intrathecally injected N-methyl-D-aspartate-induced aversive behavior in mice. Neither naloxone, an opioid receptor antagonist, phentolamine and benextramine, alpha-adrenoceptor antagonists, nor ritanserin, a 5-HT2A receptor antagonist, inhibited the calcitonin-induced anti-aversive effects. Pindolol and (--)-propranolol, non-selective antagonists of beta-adrenoceptors and 5-HT1 receptors, 1-(2-methoxyphenyl)-4-[4-(2-phethalimido) butyl]-piperazine hydrobromide (NAN-190), a 5-HT1A receptor antagonist, 3-tropanyl-3,5-dichlorobenzoate (MDL72222) and metoclopramide, 5-HT3 receptor antagonists, significantly inhibited the calcitonin-induced anti-aversive effects. (--)-Bicuculline, a GABAA receptor antagonist, phaclofen and 5-aminovaleric acid, GABAB receptor antagonists, also attenuated the calcitonin-induced anti-aversive effects. These results suggest that beta-adrenoceptor, 5-HT1A, 5-HT3, GABAA and GABAB receptors, but not alpha-adrenoceptor, opioid nor 5-HT2A receptors, are involved in the inhibitory effect of calcitonin on intrathecally injected N-methyl-D-aspartate-induced aversive behavior in mice.
为阐明降钙素的抗伤害感受作用机制，我们研究了多种神经递质受体的拮抗剂是否会改变降钙素对小鼠鞘内注射N-甲基-D-天冬氨酸诱导的厌恶行为的抑制作用。阿片受体拮抗剂纳洛酮、α-肾上腺素能受体拮抗剂酚妥拉明和苄胺苯那明，以及5-HT2A受体拮抗剂利坦色林，均未抑制降钙素诱导的抗厌恶作用。β-肾上腺素能受体和5-HT1受体的非选择性拮抗剂吲哚洛尔和（--）-普萘洛尔、5-HT1A受体拮抗剂1-（2-甲氧基苯基）-4-[4-（2-邻苯二甲酰亚胺基）丁基]-哌嗪氢溴酸盐（NAN-190）、5-HT3受体拮抗剂3-托烷-3,5-二氯苯甲酸酯（MDL72222）和甲氧氯普胺，均显著抑制了降钙素诱导的抗厌恶作用。GABAA受体拮抗剂（--）-荷包牡丹碱、GABAB受体拮抗剂巴氯芬和5-氨基戊酸，也减弱了降钙素诱导的抗厌恶作用。这些结果表明，β-肾上腺素能受体、5-HT1A、5-HT3、GABAA和GABAB受体，而非α-肾上腺素能受体、阿片受体和5-HT2A受体，参与了降钙素对小鼠鞘内注射N-甲基-D-天冬氨酸诱导的厌恶行为的抑制作用。
