CENTRAL DELTA-OPIOID RECEPTOR INTERACTIONS AND THE INHIBITION OF REFLEX URINARY-BLADDER CONTRACTIONS IN THE RAT
CENTRAL DELTA-OPIOID RECEPTOR INTERACTIONS AND THE INHIBITION OF REFLEX URINARY-BLADDER CONTRACTIONS IN THE RAT
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DOI：
10.1111/j.1476-5381.1985.tb10569.x
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发表时间：
1985-01-01
影响因子：
7.3
通讯作者：
WIRE, W
中科院分区：
文献类型：
--
作者：
DRAY, A;NUNAN, L;WIRE, W
The in vivo effects of a number of opioid agonists and antagonists were studied on the spontaneous reflex contractions of the urinary bladder recorded isometrically in the rat anesthetized with urethane. All substances were administered into the central nervous system by the intracerebroventricular (i.c.v.) or spinal intrathecal (i.t.) route. The conformationally restricted enkephalin analogs [2-D-penicillamine, 5-L-cysteine]enkephalin (DPLCE), [2-D-penicillamine, 5-L-penicillamine]enkephalin (DPLPE) and [2-D-penicillamine, 5-D-penicillamine]enkephalin (DPDE) produced dose-related inhibiton of reflex bladder contractions when administered by the i.c.v. or i.t. route. Both the novel .delta.-opioid receptor antagonist ICI 154,129 (200-600 .mu.g) [N,N-bisallyl-Tyr-Gly-Gly-.psi.-(CH2S)-Phe-Leu-OH] and ICI 174,864 (1-3 .mu.g) [N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH: Aib = .alpha.-aminoisobutyric acid] attenuated or abolished the effects of DPLCE, DPLPE and DPDPE when administered by the i.c.v. or i.t. route. The antagonism observed was selective since the equipotent inhibition produced by the .mu.-opioid receptor agonist [D-Ala2,Me-Phe4,Gly(ol)5]enkephalin (DAGO) was unaffected. Overall, ICI 154,129 was considerably weaker than ICI 174,864 and both antagonists inhibited bladder activity at doses higher than those required to demonstrate .delta.-receptor antagonism. Further studies of the agonistic effect of ICI 174,864 showed that it was sensitive to low doses of naloxone (2 .mu.g, i.c.v. or i.t.) but culd be abolished by higher (10-15 .mu.g) doses of naloxone. These observations suggested that the agonistic effect of ICI 174,864 was not mediated by .mu.-opioid receptor. .beta.-Endorphin (02-1.0 .mu.g, i.c.v.) inhibited bladder contractions but following recovery from this effect, appeared to prevent the expression of .delta.-receptor antagonism by ICI 174,864. In addition a previously subthreshold dose of ICI 174,864 now exhibited marked agonistic activity. The inhibitory effect of a submaximal dose of DPDPE was also potentiated by .beta.-endorphin under these circumstances. Supra-spinal and spinal .delta.-opioid receptors evidently are involved in the opioid-mediated inhibition of reflex bladder contractions in the rat. Moreover .beta.-endorphin may be important in regulating central .delta.-opioid receptors.
