Quito F L, Brown D R
Department of Veterinary Biology (Pharmacology Section), College of Veterinary Medicine, University of Minnesota, St. Paul.
J Pharmacol Exp Ther. 1991 Mar;256(3):833-40.
The actions of opiates in modulating ion transport across the porcine distal jejunal mucosa were examined in vitro. Opiate receptors were functionally characterized using [D-Pen2,D-Pen5]-enkephalin (DPDPE), [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and U-50,488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]-benzeneacetamide), agonists selective for delta, mu and kappa receptor types, respectively. Serosal administration of opiate agonists produced concentration-dependent decreases in basal short-circuit current (Isc. DPDPE and DAMGO also increased tissue conductance (Gt). DPDPE (EC50 = 4 nM) was 7- and 86-fold more potent in decreasing basal Isc than DAMGO and U-50,488, respectively. U-50,488 displayed the greatest efficacy in decreasing Isc. Serosal naloxone decreased DPDPE and DAMGO potencies under basal conditions with Ke values of 11 and 6 nM, respectively. DPDPE- and DAMGO-induced decreases in basal Isc were associated with increases in net Cl absorption; in addition, DAMGO produced an increase in net Na absorption. 8-Bromocyclic AMP (0.3 mM) increased Isc, decreased Gt and inhibited net Na and Cl absorptive fluxes. Selective opiate agonists decreased cyclic AMP-induced elevations in Isc with a rank order of potency (DPDPE, EC50 = 3 nM) of DPDPE greater than DAMGO greater than U-50,488. DPDPE reversed the action of cyclic AMP on Isc and Cl absorption but had no effect on net Na transport. Cyclic AMP-induced decreases in Gt were not altered by DPDPE.(ABSTRACT TRUNCATED AT 250 WORDS)
在体外研究了阿片类药物对猪空肠远端黏膜离子转运的调节作用。使用[D-青霉胺2，D-青霉胺5]-脑啡肽（DPDPE）、[D-丙氨酸2，N-甲基苯丙氨酸4，甘氨酸5-醇]-脑啡肽（DAMGO）和U-50,488（反式-3,4-二氯-N-甲基-N-[2-(1-吡咯烷基)-环己基]-苯乙酰胺）对阿片受体进行功能表征，它们分别是δ、μ和κ受体类型的选择性激动剂。向浆膜侧给予阿片类激动剂会使基础短路电流（Isc）呈浓度依赖性降低。DPDPE和DAMGO还会增加组织电导（Gt）。DPDPE（EC50 = 4 nM）降低基础Isc的效力分别比DAMGO和U-50,488高7倍和86倍。U-50,488在降低Isc方面显示出最大的效力。浆膜侧给予纳洛酮会在基础条件下降低DPDPE和DAMGO的效力，Ke值分别为11 nM和6 nM。DPDPE和DAMGO诱导的基础Isc降低与净Cl吸收增加有关；此外，DAMGO会使净Na吸收增加。8-溴环磷酸腺苷（0.3 mM）会增加Isc，降低Gt，并抑制净Na和Cl吸收通量。选择性阿片类激动剂会降低环磷酸腺苷诱导的Isc升高，效力顺序为（DPDPE，EC50 = 3 nM）DPDPE大于DAMGO大于U-50,488。DPDPE可逆转环磷酸腺苷对Isc和Cl吸收的作用，但对净Na转运无影响。环磷酸腺苷诱导的Gt降低不受DPDPE影响。（摘要截断于250字）
