Opposite interactions between alpha- and beta-endorphin fragments with dopamine mediated responses on the rat rectum in vitro.

Dopamine causes a dose-dependent contraction of the rat rectum in vitro followed by a relaxation. This contraction can be inhibited by apomorphine and phenylephrine. This inhibition can be attenuated by the beta-endorphin (beta E) fragments 2-17 (des-Tyr1-gamma-endorphin, DT gamma E) and 6-17 (des-enkephalin-gamma-endorphin, DE gamma E). beta E 6-17 seems to be the shortest sequence with full activity in this respect since a shorter fragment (beta E 10-17) was less effective. The atypical neuroleptics oxypertine, sulpiride, and clozapine, the classic neuroleptic haloperidol and metoclopramide have a similar action to DE gamma E. The peptides and atypical neuroleptics do not affect the dopamine response per se while the classic neuroleptics haloperidol and metoclopramide enhance the dopamine response. The effects of the alpha-type endorphins are opposite to those of the gamma-type endorphins, since des-Tyr1-alpha-endorphin (DT alpha E, beta E 2-16) and des-enkephalin-alpha-endorphin (DE alpha E, beta E 6-16) enhance the phenylephrine-induced decreased responsiveness to dopamine. Structure-activity studies revealed that the active moiety of the alpha-endorphin fragments probably resides in the 6-9 region. In addition the alpha-type endorphins directly inhibit the dopamine response. It is concluded that the rat rectum may be used to analyse neuroleptic-like action. In this model alpha- and gamma-endorphin fragments may directly or indirectly influence the interaction of dopamine with the rectum. Because of the strong similarities between the effects of gamma-type endorphins and that of neuroleptics the results support the purported neuroleptic-like action of gamma-type endorphins. The influence of alpha-type endorphins and gamma-type endorphins on the apomorphine or phenylephrine induced decreased responsiveness to dopamine, although opposite, seems to be mediated by an influence on different dopamine sensitive systems.