Summary
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.
Similar content being viewed by others
References
De Wied D (1978) Psychopathology as a neuropeptide dysfunction. In: Van Ree JM, Terenius L (eds) Characteristics and function of opioids. Elsevier/North-Holland Biomedical Press, Amsterdam, pp 113–122
De Wied D, Kovacs GL, Bohus B, Van Ree JM, Greven HM (1978) Neuroleptic activity of the neuropeptide β-LPH62–77 ([des-Tyr1]-γ-endorphin; DTγE). Eur J Pharmacol 49:427–436
De Wied D, Van Ree JM, Greven HM (1980) Neuroleptic-like activity of peptides related to (des-tyr1)-γ-endorphin: structure activity studies. Life Sci 26:1275–1279
LeMoal M, Koob GF, Bloom FE (1979) Endorphins and extinction: differential actions on appetitive and adversive tasks. Life Sci 24:1631–1636
Nijkamp FP, Van Ree JM (1978) Effects of endorphins on different parts of the gastrointestinal tract in vitro. In: Van Ree JM, Terenius L (eds) Characteristics and function of opioids. Elsevier/North-Holland Biomedical Press, Amsterdam, pp 179–180
Nijkamp FP, Van Ree JM (1980) Effects of endorphins on different parts of the gastrointestinal tract of rat and guinea-pig in vitro. Br J Pharmacol 68:599–606
Van Ree JM (1982) Non-opiate β-endorphin fragments and dopamine. II. β-Endorphin 2-9 enhances apomorphine-induced stereotypy following subcutaneous and intra-striatal injection. Neuropharmacology (in press)
Van Ree JM, Verhoeven WMA, Van Praag HM, De Wied D (1978) Antipsychotic action of (des-Tyr1)-γ-endorphin (β-LPH67–77). In Van Ree JM, Terenius L (eds) Characteristics and function of opioids. Elsevier/North-Holland Biomedical Press, Amsterdam, pp 181–184
Van Ree JM, Bohus B, De Wied D (1980a) Similarity between behavioral effects of des-tyrosine-γ-endorphin and haloperidol and of α-endorphin and amphetamine. In: Leong Way E (ed) Endogenous and exogenous opiate agonists and antagonists. Oxford, Pergamon Press, pp 459–462
Van Ree JM, De Wied D, Verhoeven WMA, Van Praag HM (1980b) Antipsychotic effect of γ-type endorphins in schizophrenia. Lancet II:1363–1365
Van Ree JM, Innemee H, Louwrens JW, Kahn RS, De Wied D (1982a) Non-opiate β-endorphin fragments and dopamine. I. The neuroleptic-like γ-endorphin fragments interfere with behavioral effects elicited by low doses of apomorphine. Neuropharmacology (in press)
Van Ree JM, Caffé AR, Wolterink G (1982b) Non-opiate β-endorphin fragments and dopamine. III. γ-Type endorphins and various neuroleptics counteract the hypoactivity elicited by intra-accumbens injection of apomorphine. Neuropharmacology (in press)
Verhoeven WMA, Van Praag HM, Van Ree JM, De Wied D (1979) Improvement of schizophrenic patients treated with (Des-Tyr1)-γ-endorphin (DTγE). Arch Gen Psychiatry 36:294–298
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nijkamp, F.P., van Ree, J.M., Nijssen, J.G. et al. Opposite interactions between α- and β-endorphin fragments with dopamine mediated responses on the rat rectum in vitro. Naunyn-Schmiedeberg's Arch. Pharmacol. 321, 213–217 (1982). https://doi.org/10.1007/BF00505488
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00505488