Heijna M H, Bakker J M, Hogenboom F, Mulder A H, Schoffelmeer A N
Department of Pharmacology, Free University, Medical Faculty, Amsterdam, Netherlands.
Eur J Pharmacol. 1992 Dec 15;229(2-3):197-202. doi: 10.1016/0014-2999(92)90555-i.
In slices of rat nucleus accumbens, olfactory tubercle, frontal cortex and mediobasal hypothalamus exposed to dopamine (DA), the activation of DA D1 receptors stimulated cyclic AMP (cAMP) formation whereas, in nucleus accumbens slices only, activation of D2 receptors appeared to inhibit D1 receptor-stimulated adenylate cyclase at the same time. Activation of mu-opioid receptors by [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO; 1 microM), but not of delta-opioid receptors by 1 microM [D-Pen2,D-Pen5]enkephalin (DPDPE), inhibited (by 35-40%) DA-stimulated cAMP production in slices of nucleus accumbens and olfactory tubercle. When adenylate cyclase was stimulated by selective D1 receptor activation, i.e. by DA in the presence of (-)-sulpiride, DPDPE reduced cAMP formation (by about 45%) in nucleus accumbens slices but not in slices of the other brain regions. The kappa-agonist, U 50,488, did not affect DA- or D1 receptor-stimulated adenylate cyclase activity in any of the brain regions. Preincubation of nucleus accumbens slices with the irreversible delta-ligand, fentanyl isothiocyanate (FIT; 1 microM), not only antagonized the inhibitory effect of DPDPE but also prevented the antagonism by naloxone of the inhibitory effect of DAMGO. Therefore, in nucleus accumbens opioids may inhibit DA-sensitive adenylate cyclase through activation of a mu/delta-opioid receptor complex, whereas in olfactory tubercle mu-receptors appear to mediate the inhibition of adenylate cyclase activity. Opioids do not seem to affect DA-stimulated cAMP formation in frontal cortex and mediobasal hypothalamus.
在暴露于多巴胺（DA）的大鼠伏隔核、嗅结节、额叶皮质和下丘脑中间基底部切片中，DA D1受体的激活刺激了环磷酸腺苷（cAMP）的形成，而仅在伏隔核切片中，D2受体的激活似乎同时抑制了D1受体刺激的腺苷酸环化酶。[D-丙氨酸2，甲硫氨酸苯丙氨酸4，甘醇5]脑啡肽（DAMGO；1 microM）激活μ-阿片受体，但1 microM [D-青霉胺2，D-青霉胺5]脑啡肽（DPDPE）激活δ-阿片受体，均未抑制（35%-40%）伏隔核和嗅结节切片中DA刺激的cAMP产生。当腺苷酸环化酶通过选择性D1受体激活（即在存在（-）-舒必利的情况下由DA激活）时，DPDPE降低了伏隔核切片中cAMP的形成（约45%），但在其他脑区切片中未降低。κ-激动剂U 50,488在任何脑区均不影响DA或D1受体刺激的腺苷酸环化酶活性。用不可逆的δ-配体异硫氰酸芬太尼（FIT；1 microM）预孵育伏隔核切片，不仅拮抗了DPDPE的抑制作用，还阻止了纳洛酮对DAMGO抑制作用的拮抗。因此，在伏隔核中，阿片类药物可能通过激活μ/δ-阿片受体复合物抑制DA敏感的腺苷酸环化酶，而在嗅结节中，μ-受体似乎介导了腺苷酸环化酶活性的抑制。阿片类药物似乎不影响额叶皮质和下丘脑中间基底部中DA刺激的cAMP形成。
