gamma-endorphin and des-enkephalin-gamma-endorphin

The pharmacological actions of gamma-type endorphins show similarities to those of the neuroleptics. Two fragments of gamma-endorphin (beta-LPH 61-77) were therefore tested in patients with schizophrenic and schizo-affective psychoses who had shown an insufficient response to neuroleptics. The fragments were DT gamma E (beta-LPH 62-77) and DE gamma E (beta-LPH 66-77). Some of the patients studied responded favorably to this treatment. A number of criteria of differentiation between responders and nonresponders are discussed. The influence of DT gamma E on the central DA metabolism differs from that of the neuroleptics. It is therefore conceivable that gamma-type endorphins represent a different principle of action. The therapeutic efficacy of these compounds lends support to the hypothesis that disorders of central endorphin metabolism may play a role in the pathogenesis of psychoses of the schizophrenic type.

Topics: beta-Endorphin; Brain; Clinical Trials as Topic; Dopamine; Double-Blind Method; Endorphins; gamma-Endorphin; Humans; Peptide Fragments; Psychotic Disorders; Receptors, Dopamine; Schizophrenia; Schizophrenic Psychology

Topics: Adult; beta-Endorphin; Brain; Clinical Trials as Topic; Dopamine; Double-Blind Method; Endorphins; Female; gamma-Endorphin; Humans; Male; Middle Aged; Peptide Fragments; Schizophrenia

Opioid peptides have been shown to enhance peripheral blood lymphocyte natural killer (NK) cell function. In this study, we report that certain non-opioid fragments of beta-endorphin (2-16, 2-17, and 6-17) enhance NK activity with peak dose responses seen at 10(-12) to 10(-15) concentrations. This effect can be inhibited by naloxone. We conclude that non-opioid fragments of beta-endorphin are more potent than either beta- or gamma-endorphin in enhancing human lymphocyte NK activity.

Topics: beta-Endorphin; Endorphins; gamma-Endorphin; Humans; Killer Cells, Natural; Naloxone; Peptide Fragments

Neuroleptic drugs increase the level of alpha-melanotropin (alpha-MSH) in the blood of the rat. We have investigated whether neuroleptic-like peptides, the gamma-type endorphins, also affect alpha-MSH release. A structure-activity study revealed that (des-enkephalin)-gamma-endorphin (DE gamma E, beta-LPH-(66-77), beta-endorphin-(6-17)) is able to increase plasma alpha-MSH levels after intracerebroventricular injection, while the longer gamma-type endorphins, i.e. gamma E (beta-LPH-(61-77)), beta-endorphin-(1-17)), and DT gamma E (beta-LPH-(62-77), beta-endorphin-(2-17)) were without effect in the dosage used. A dose-response study revealed a more or less bell-shaped relationship for the effect of DE gamma E on plasma alpha-MSH levels. The effect of DE gamma E could not be counteracted by apomorphine or naloxone. The observations indicate that DE gamma E increases plasma alpha-MSH levels in a way distinct from that of haloperidol and the opiate peptide beta-endorphin. On the other hand, a time-course of plasma alpha-MSH levels after DE gamma E administration resembled the one which has been seen after haloperidol injection. From experiments performed on pituitary neurointermediate lobes incubated in vitro, it seems not likely that DE gamma E acts directly on the dopamine receptors of the pituitary in affecting alpha-MSH release. In conclusion, it appears that DE gamma E affects alpha-MSH levels in plasma in a way distinct from that of the neuroleptic drug haloperidol and of the opiate-peptide beta-endorphin.

Topics: Animals; Antipsychotic Agents; Apomorphine; beta-Endorphin; Dose-Response Relationship, Drug; Endorphins; gamma-Endorphin; Haloperidol; Injections, Intraventricular; Male; Melanocyte-Stimulating Hormones; Naloxone; Pituitary Gland, Anterior; Rats; Rats, Inbred Strains

Injection of small doses of apomorphine, bromocriptine and the new ergoline compound, GYKI-32887 into the nucleus accumbens decreased locomotor activity when rats were tested in a small open field. This effect was observed following injection of 1 pg of these substances; GYKI-32887 being more potent than bromocriptine. The hypolocomotion induced by the ergoline compound could be prevented by local pretreatment with haloperidol (30 pg), fluphenazine (30 pg), sulpiride (10 pg) or desenkephalin -gamma-endorphin (DE gamma E; 100 pg). Large doses of apomorphine and amphetamine, injected into the nucleus accumbens, increased locomotor activity. This behavioural response was antagonized by pretreatment with haloperidol (30 pg), but not with sulpiride (10 pg) or DE gamma E (100 pg or 10 ng). It is concluded that two dopaminergic receptor systems exist in the nucleus accumbens with different sensitivity to apomorphine. One of these receptor systems, which is activated by small doses of apomorphine and ergoline compounds, can be blocked by classical and atypical neuroleptics and by the neuroleptic-like peptide DE gamma E. This may be of relevance to the antipsychotic action of these substances.

Topics: Amphetamine; Animals; Apomorphine; Behavior, Animal; beta-Endorphin; Bromocriptine; Dopamine; Endorphins; Ergolines; Fluphenazine; gamma-Endorphin; Haloperidol; Male; Motor Activity; Nucleus Accumbens; Rats; Rats, Inbred Strains; Septal Nuclei; Sulpiride

In order to investigate whether genetic factors are involved in the response of schizophrenic patients to treatment with gamma-type endorphins, we typed 32 Dutch schizophrenic patients for the HLA-A, -B, -C and -DR antigens. The total patient group showed an increase of HLA-Bw4 and HLA-Cw1. A subgroup of 20 paranoid patients showed an increase of HLA-Cw1 and a significant heterogeneity for the HLA-C locus. In 16 patients who responded moderately or markedly to treatment with gamma-type endorphins, an increase of HLA-B15/Cw3 and a decrease of HLA-B17 were found as compared to 16 patients with no or a slight response. Moreover, HLA-B15 was particularly increased in those patients who responded markedly and remained free of psychotic symptoms for a period of at least 6 months after treatment with gamma-type endorphins (RR = 24.6, Puncorr. = 0.0015). Our results suggest that genetic factors coded for within the HLA region are associated with paranoid schizophrenia, and that HLA-B15/Cw3 is associated with a marked and prolonged response to treatment with gamma-type endorphins.

Topics: beta-Endorphin; Endorphins; gamma-Endorphin; HLA Antigens; HLA-B Antigens; HLA-B15 Antigen; HLA-C Antigens; Humans; Peptide Fragments; Schizophrenia

Topics: Animals; Antipsychotic Agents; Behavior, Animal; beta-Endorphin; Dopamine; Double-Blind Method; Endorphins; gamma-Endorphin; Humans; Peptide Fragments; Psychiatric Status Rating Scales; Psychotic Disorders; Rats; Receptors, Dopamine; Receptors, Opioid; Schizophrenia; Schizophrenic Psychology