Opiate receptor binding studies in the mouse vas deferens exhibiting tolerance without dependence

Abstract

The apparent lack of dependence in highly opiate-tolerant isolated mouse vas deferens may conflict with unitary theories postulating a common biochemical mechanism for both phenomena. Therefore, attention focused on binding sites of the opiate receptors which in this tissue are located presynaptically. Binding studies conducted with homogenate of highly tolerant vasa deferentia revealed no significant different results as compared to naive tissues. Further studies examined the effect of guanine nucleotide on opiate receptor interaction. Apparently, mu-, delta- and kappa-opiate receptors in the mouse vas deferens proved resistant to the regulatory action of guanine nucleotide in naive and tolerant tissues. From these experiments, it is concluded that the binding characteristics of opiate receptors in the mouse vas deferens do not change with chronic activation. In addition, the lack of an effect of guanine nucleotide on opiate binding leads to the suggestion that binding sites are not coupled to adenylate cyclase in this tissue. Taken together, these findings draw the attention to the coupling mechanism of opiate receptors in the mouse vas deferens which may play a key role in the adaptational mechanisms following chronic opiate exposure.