Modulatory effect of endogenous and exogenous opioids on the excitatory reflex pathway of the rat ileum

Abstract

The ascending excitatory reflex is part of the peristaltic reflex, an important participant in intestinal propulsion. The aim of this study was to characterize the role of different opioid receptors in the ascending reflex through exogenous application of non-selective (Met-enkephalin) and selective opioid agonists (mu-PLO17, delta-DPDPE, kappa-U-50, 488) as well as selective opioid receptor antagonists (mu: CTOP-NH2, delta: ICI-174,864, kappa: Nor-Binaltorphimine). Metenkephalin (IC50: 0.06 μM) and morphine (IC50: 1.8 μM) inhibited the ascending reflex response concentration-dependently. Both the mu-selective agonist PLO17 (IC50: 0.83 μM, n =11) and the kappa-selective agonist U-50,488 (IC50: 0.68 μM, n =8) concentration-dependently inhibited the magnitude of the ascending contractile reflex response, whereas the delta-agonist DPDPE (10–10–10–6M) had no significant effect. In contrast, the latency of the response (time interval between start of the stimulus and onset of the contraction) was significantly prolonged by PLO17 > morphine > Met-enkephalin > DPDPE, whereas U-50,488 showed no effect. When the effect of the receptor-specific antagonists was tested, only CTOP-NH2and Nor-BNI caused a significant increase of the contractile response, whereas ICI-174 864 was ineffective. On the other hand, CTOP-NH2> ICI-174 864 decreased the latency significantly but the kappa-receptor agonist Nor-BNI had no influence. Thus, mu- and kappa-receptors seem to be involved in regulating the contraction strength of the ascending reflex, whereas both mu- and delta-receptors seem to be involved in the timing of the reflex response.