- Email: [email protected]
Metabolism of cerebral peptides of physiological importance
374
FREE COMMUNICATIONS
Insulin levels were examined after the glucose load by the radioimmunological assay of Hales and Randle. The psychopathological features were examined through a Wittenborn Rating Scale. The metabolic and psychological examinations were performed twice before the beginning of the therapy, at 48 h intervals, and then after 10, 20 and 30 days of therapy. The results are indicative of the presence of a chemical diabetes in a significantly high percentage of patients, as demonstrated by markedly elevated insulinemic and glycemic peak values, delayed insulinemic and glycemic peak values, and prolonged hyperglycemia and hyperinsulinemia (Fig. 1A and B). The response to exogenously administered insulin was normal rather than excessive. Haloperidol treatment did not modify these results. The biochemical data seem to correlate with the presence of specific psychopathological symptomatology, such as severe mental deterioration, apathy and withdrawal from reality. A possible common basis for both the biochemical and psychological impairments is proposed. A noradrenaline insufficiency, which may be related to the presence in the CNS of an excessive amount of 6-OHDA, could explain the reported pathological data.
Metabolism of cerebral peptides of physiological importance ABELLAJTHA AND AMOSNEIDLE- New York State Research Institute for Neurochemistry and Drug Addiction, Ward's Island, New York, N. Y . 10035 (U.S.A.) Peptides with even a small number of amino acid residues present an almost unlimited array of sizes, shapes, and electrical charge distributions. Small peptides with such properties could play an important role in information transfer in brain by interaction with appropriate receptors. The observations that hypothalamic releasing factors can influence mood and behavior without endocrine mediation support this concept. We have shown that endogenous peptidase activity might be involved in the release and inactivation of these agents. Another example of peptide specificity has been recently reported'. Carnosine (p-alanylhistidine) is present in the olfactory bulb of the mouse at about 2 pmoleslg, a concentration 100-fold higher than its y-aminobutyryl analog, homocarnosine. This is in marked contrast to other brain areas in which homocarnosine predominates. A similar distribution was found in rat brain. In a single sample of human bulb, carnosine and homocarnosine were present in nearly equal concentration. Experiments with radioactive precursors in vitro indicate that carnosine is synthesized in olfactory bulb by an enzyme which incorporates p-alanine, but not GABA, into peptide linkage. Therefore, this enzyme appears different from the homocarnosine synthetase of cerebral hemisphere which does not distinguish between these two substrates. The preferential distribution of carnosine as well as its rapid turnover in bulb suggests an important functional role for this dipeptide. Such a role has been independently proposed2 based on the decrease of the
FREE COMMUNICATIONS
375
carnosine concentration in mouse olfactory bulb following chemical ablation of the afferent olfactory neurons of the nasal mucosa. 1 Proc. Amer. Soc. Neurochem., 5 (1974) 169. 2 MARGOLIS, F. L., Science, 184 (1974) 909.
Delta-9-tetrahydrocannabinolaction and neuronal membrane-bound enzymes
J. J. GHOSH,M. K. PODDAR,D. NAGAND B . BISWAS - Department of Biochemistry, University College of Science, Calcutta University, Calcutta-19 (India) Delta-9-tetrahydrocannabinol (A-9-THC), the major pharmacologically active component of cannabis, produces characteristic changes in the activities of membranebound enzymes of rat brain, under both in vivo and in vitro conditions. Acute A-9THC administration (10 mg and 50 mg/kg, i.p.) produced stimulation of acetylcholine esterase and glutamine synthetase activities in both synaptosomal and microsoma1 fractions, whereas the Na+-K+-ATPase activity in synaptosomes was inhibited and in microsomal fractions was stimulated under the same experimental conditions. Chronic treatment (10 mg/kg, i.p., 30 days) produced no significant changes in the activities of these enzymes. M ) produced inhibitory In vitro treatment with A-9-THC (lo-’ M and effects on both synaptosomal and microsomal Na+-K+-ATPaseactivities, stimulatory effects on synaptosomal activities, and stimulatory effects on synaptosomal and microsomal glutamine synthetase activities. The activity of acetylcholine esterase was stimulated in synaptosomes and inhibited in microsomal fractions.
The effect of exposure to two odorous compounds (pheromones) on an assessment of people test
J. J. COWLEY AND B. W. L. BROOKSBANK - Department of Psychology, The Queen’s University, Bevast ( N . Ireland) Work has been carried out on the effect of exposing people, for a short period of time, to a mixture of short-chain fatty acids and to androstenol (5-androst-16-en3-01). The compounds were selected as they have been reported as having pheromonelike properties. Subjects were exposed to one or other of the compounds, and a third sample acted as a control. A test was designed which required participants to express favorable or unfavorable opinions about the suitability of a number of applicants, of both sexes, for a position of responsibility. A brief character sketch was provided as a basis for making judgments. The results show that women exposed to the presence of the fatty acids and the androstenol are not affected in their assessments of applicants of their own sex, but that exposure is accompanied by a change in their assessment
FREE COMMUNICATIONS
Insulin levels were examined after the glucose load by the radioimmunological assay of Hales and Randle. The psychopathological features were examined through a Wittenborn Rating Scale. The metabolic and psychological examinations were performed twice before the beginning of the therapy, at 48 h intervals, and then after 10, 20 and 30 days of therapy. The results are indicative of the presence of a chemical diabetes in a significantly high percentage of patients, as demonstrated by markedly elevated insulinemic and glycemic peak values, delayed insulinemic and glycemic peak values, and prolonged hyperglycemia and hyperinsulinemia (Fig. 1A and B). The response to exogenously administered insulin was normal rather than excessive. Haloperidol treatment did not modify these results. The biochemical data seem to correlate with the presence of specific psychopathological symptomatology, such as severe mental deterioration, apathy and withdrawal from reality. A possible common basis for both the biochemical and psychological impairments is proposed. A noradrenaline insufficiency, which may be related to the presence in the CNS of an excessive amount of 6-OHDA, could explain the reported pathological data.
Metabolism of cerebral peptides of physiological importance ABELLAJTHA AND AMOSNEIDLE- New York State Research Institute for Neurochemistry and Drug Addiction, Ward's Island, New York, N. Y . 10035 (U.S.A.) Peptides with even a small number of amino acid residues present an almost unlimited array of sizes, shapes, and electrical charge distributions. Small peptides with such properties could play an important role in information transfer in brain by interaction with appropriate receptors. The observations that hypothalamic releasing factors can influence mood and behavior without endocrine mediation support this concept. We have shown that endogenous peptidase activity might be involved in the release and inactivation of these agents. Another example of peptide specificity has been recently reported'. Carnosine (p-alanylhistidine) is present in the olfactory bulb of the mouse at about 2 pmoleslg, a concentration 100-fold higher than its y-aminobutyryl analog, homocarnosine. This is in marked contrast to other brain areas in which homocarnosine predominates. A similar distribution was found in rat brain. In a single sample of human bulb, carnosine and homocarnosine were present in nearly equal concentration. Experiments with radioactive precursors in vitro indicate that carnosine is synthesized in olfactory bulb by an enzyme which incorporates p-alanine, but not GABA, into peptide linkage. Therefore, this enzyme appears different from the homocarnosine synthetase of cerebral hemisphere which does not distinguish between these two substrates. The preferential distribution of carnosine as well as its rapid turnover in bulb suggests an important functional role for this dipeptide. Such a role has been independently proposed2 based on the decrease of the
FREE COMMUNICATIONS
375
carnosine concentration in mouse olfactory bulb following chemical ablation of the afferent olfactory neurons of the nasal mucosa. 1 Proc. Amer. Soc. Neurochem., 5 (1974) 169. 2 MARGOLIS, F. L., Science, 184 (1974) 909.
Delta-9-tetrahydrocannabinolaction and neuronal membrane-bound enzymes
J. J. GHOSH,M. K. PODDAR,D. NAGAND B . BISWAS - Department of Biochemistry, University College of Science, Calcutta University, Calcutta-19 (India) Delta-9-tetrahydrocannabinol (A-9-THC), the major pharmacologically active component of cannabis, produces characteristic changes in the activities of membranebound enzymes of rat brain, under both in vivo and in vitro conditions. Acute A-9THC administration (10 mg and 50 mg/kg, i.p.) produced stimulation of acetylcholine esterase and glutamine synthetase activities in both synaptosomal and microsoma1 fractions, whereas the Na+-K+-ATPase activity in synaptosomes was inhibited and in microsomal fractions was stimulated under the same experimental conditions. Chronic treatment (10 mg/kg, i.p., 30 days) produced no significant changes in the activities of these enzymes. M ) produced inhibitory In vitro treatment with A-9-THC (lo-’ M and effects on both synaptosomal and microsomal Na+-K+-ATPaseactivities, stimulatory effects on synaptosomal activities, and stimulatory effects on synaptosomal and microsomal glutamine synthetase activities. The activity of acetylcholine esterase was stimulated in synaptosomes and inhibited in microsomal fractions.
The effect of exposure to two odorous compounds (pheromones) on an assessment of people test
J. J. COWLEY AND B. W. L. BROOKSBANK - Department of Psychology, The Queen’s University, Bevast ( N . Ireland) Work has been carried out on the effect of exposing people, for a short period of time, to a mixture of short-chain fatty acids and to androstenol (5-androst-16-en3-01). The compounds were selected as they have been reported as having pheromonelike properties. Subjects were exposed to one or other of the compounds, and a third sample acted as a control. A test was designed which required participants to express favorable or unfavorable opinions about the suitability of a number of applicants, of both sexes, for a position of responsibility. A brief character sketch was provided as a basis for making judgments. The results show that women exposed to the presence of the fatty acids and the androstenol are not affected in their assessments of applicants of their own sex, but that exposure is accompanied by a change in their assessment