The Differential Effects of a Selective Kappa-Opioid Receptor Agonist, U50488, in Guinea Pig Heart Tissues

Abstract

The differential effects of a selective kappa- (κ-) opioid receptor agonist, U50488, were elucidated by monitoring the contraction of isolated guinea pig atrial and ventricular muscles. In electrically driven left atria, U50488 in nanomolar concentration range decreased the contractile force. Norbinaltorphimine (norBNI), a selective κ-receptor antagonist, and pertussis toxin (PTX) abolished the negative inotropic effect of U50488. In contrast, the inhibitory effect was not affected by the pretreatment of atropine or propranolol. Even though U50488 exerted a negative inotropic effect in the left atrium, it did not affect the contractile force of the right atrium and ventricles paced at 2 Hz. Similarly, the beating rate of the spontaneously beating right atrium was also unaffected by U50488. These results indicate that the activation of κ-opioid receptors can only produce negative inotropic effect in left atria via activation of PTX-sensitive G protein in guinea pigs. The absence of negative inotropic effects in right atria and ventricles suggests that there may be a greater distribution of functional κ-opioid receptors in guinea pig left atria than in right atria and ventricles, and the distribution of the receptors may be species-specific.

Opioid receptor activation modulates the calcium current in the cochlear outer hair cells of the rat

“…Although our results indicate that κ receptor agonist actions are selective and can be blocked by its specific antagonists (Hung et al, 2015;Vonvoigtlander et al, 1983), the endogenous opiates like endomorphin-1 and dynorphin-B inhibit the response to acetylcholine (ACh) in IHC of the rat, probably acting directly in ACh A Kruskal-Wallis test showed that the concentration of U-50488 significantly affected the current amplitude (H = 24.6, P = 0.00012, df = 3), followed by the Tukey's test, demonstrated that all the groups were different from the control (P = 0.03, 0.0004, 0.00005, respectively); within groups, there was a tendency but no significant difference. Inhibitory action of U-50488 is already significant at concentrations as low as 10 nM (P < 0.05).…”

“…Although our results indicate that κ receptor agonist actions are selective and can be blocked by its specific antagonists (Hung et al, 2015; Vonvoigtlander et al, 1983), the endogenous opiates like endomorphin‐1 and dynorphin‐B inhibit the response to acetylcholine (ACh) in IHC of the rat, probably acting directly in ACh receptors (Lioudyno et al, 2002). The κ receptor agonists U‐50488 and pentazocine used at large concentrations (≅100 mM) may significantly modify the auditory nerve compound action potential.…”

Opioids in Remote Ischemic Preconditioning-Induced Cardioprotection

“…Exogenous and endogenous opioids exhibit pharmacological effects via interacting with G-protein-coupled opioid receptor system, encompassing δ-, κ-, and µ-opioid receptors. 57,58 All the subtypes of opioid receptors are widely distributed in the atria and the ventricles of the heart for initiating a cascade of events involved in cardioprotection against sustained ischemia–reperfusion injury. 59,60 The heart is a complex neuroendocrine organ that synthesizes endogenous opioids in the heart that may act in autocrine or paracrine fashion to modulate functioning of the heart.…”