Steardo L, Monteleone P, d'Istria M, Serino I, Maj M, Cuomo V
Department of Pharmacology, School of Medicine, University of Bari, Bari, Italy.
J Neurochem. 1996 Jul;67(1):287-93. doi: 10.1046/j.1471-4159.1996.67010287.x.
Because sigma receptors are richly concentrated in the rat pineal gland, the present study was performed to investigate their possible role in the modulation of melatonin production. To this purpose, we assessed in vivo the effects of the sigma-receptor ligands 1,3-di(2-tolyl)guanidine and (+)-N-allylnormetazocine on the rat pineal gland activity during either the daytime or the nighttime. Compared with vehicle, 1,3-di(2-tolyl)guanidine and (+)-N-allylnormetazocine potentiated the enhancement of N-acetyltransferase activity and pineal melatonin content induced by isoproterenol administration during the daytime, whereas they did not affect the diurnal basal biosynthetic activity of the gland. Conversely, at night, 1,3-di(2-tolyl)guanidine and (+)-N-allylnormetazocine enhanced significantly the physiological increases in both pineal N-acetyltransferase activity and melatonin levels. This enhancement was prevented by pretreatment with rimcazole, a specific sigma-receptor antagonist. These findings suggest that, in rats, the activation of pineal sigma-receptor sites does not affect the biosynthetic activity of the pineal gland during daytime, whereas it potentiates the production of melatonin when the gland is noradrenergically stimulated either by isoproterenol administration or by the endogenously released norepinephrine at nighttime.
由于σ受体在大鼠松果体中高度富集，因此进行本研究以探讨其在调节褪黑素分泌中的可能作用。为此，我们在白天或夜间评估了σ受体配体1,3 - 二（2 - 甲苯基）胍和（+）-N - 烯丙基去甲左啡诺对大鼠松果体活性的影响。与溶剂对照组相比，1,3 - 二（2 - 甲苯基）胍和（+）-N - 烯丙基去甲左啡诺增强了白天异丙肾上腺素给药诱导的N - 乙酰转移酶活性增强和松果体褪黑素含量增加，而它们并未影响该腺体的昼夜基础生物合成活性。相反，在夜间，1,3 - 二（2 - 甲苯基）胍和（+）-N - 烯丙基去甲左啡诺显著增强了松果体N - 乙酰转移酶活性和褪黑素水平的生理性升高。这种增强作用可被特异性σ受体拮抗剂利美唑预处理所阻断。这些发现表明，在大鼠中，白天激活松果体σ受体位点不影响松果体的生物合成活性，而在夜间当腺体受到异丙肾上腺素给药或内源性释放的去甲肾上腺素的去甲肾上腺素能刺激时，它会增强褪黑素的分泌。
