Opposite interactions between α- and β-endorphin fragments with dopamine mediated responses on the rat rectum in vitro

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Abstract
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 β-endorphin (βE) fragments 2–17 (des-Tyr1-γ-endorphin, DTγE) and 6-17 (des-enkephalin-γ-endorphin, DEγE). βE 6-17 seems to be the shortest sequence with full activity in this respect since a shorter fragment (βE 10-17) was less effective. The atypical neuroleptics oxypertine, sulpiride, and clozapine, the classic neuroleptic haloperidol and metoclopramide have a similar action to DEγE. 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 α-type endorphins are opposite to those of the γ-type endorphins, since des-Tyr1-α-endorphin (DTαE, βE 2-16) and des-enkephalin-α-endorphin (DEαE, βE 6-16) enhance the phenylephrine-induced decreased responsiveness to dopamine. Structure-activity studies revealed that the active moiety of the α-endorphin fragments probably resides in the 6–9 region. In addition the α-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 α- and γ-endorphin fragments may directly or indirectly influence the interaction of dopamine with the rectum. Because of the strong similarities between the effects of γ-type endorphins and that of neuroleptics the results support the purported neurolepticlike action of γ-type endorphins. The influence of α-type endorphins and γ-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.