Three histamine receptors have been described, H 1, H 2 and H 3. Histaminergic neurons are located almost exclusively in the ventral posterior hypothalamus and project throughout the entire CNS. This amine does not qualify as a transmitter according to the rigid definitions outlined earlier, since no evidence exists for either its release on stimulation of a neuronal tract, nor is there a rapid reuptake mechanism or enzymatic catabolism to terminate its activity.
Serotonin is initially catabolized by the mitochondrial enzyme monoamine oxidase to yield the intermediate 5-hydroxyindoleacetaldehyde, which is rapidly converted to 5-hydroxyindoleacitic acid by the enzyme aldehyde dehydrogenase.ĭecarboxylation of the amino acid histidine results in the formation of histamine, a still questionable neurotransmitter. The catabolism of dopamine is shown in Fig. The atypical neuroleptic drug clozapine, however, exhibits a greater affinity for the D 4 receptor, dopaminergic transmission in the nucleus accumbens, involving both D 1 and D 2 receptors, is believed to be involved in the reward activity of abused drugs such as cocaine. Arising from the observation that a correlation existed between therapeutic doses of antipsychotic drugs and inhibition of binding of dopamine receptor antagonists, the D 2 receptor has been fingered in the pathophysiology of schizophrenia. All the receptors are coupled to G proteins as their second messenger. Currently the subtypes consist of D 1 through D 5 with the possibility of a D 6.
Initially, dopamine receptors were classified as D 1 or D 2. The nigrostriatal pathway is particularly important since its degeneration is involved in Parkinson's disease. Dopaminergic terminals are found in the basal ganglia, the nucleus acumbens, the olfactory tubercle, the amygdala, and the frontal cortex. Dopamine cells originate in the substantia nigra, ventral tegmental area, caudal thalamus, periventricular hypothalamus, and olfactory bulb. It is now clear, however, that dopamine is a major player in the CNS with its implication in Parkinson's disease and in schizophrenia. The culture medium from the AtT-20 mouse pituitary tumor cells contained approximately equimolar amounts of ACTH-related peptides and endorphin-related peptides.At one time dopamine was thought to be just an intermediate in the conversion of tyrosine to noradrenaline. The 3500 dalton endorphin is similar to β-endorphin in size and structure. Most of the peptide cleaved from 31,000 dalton ACTH when it is converted to 23,000 dalton ACTH could be precipitated by endorphin antisera this 11,700 dalton endorphin molecule is similar to the pituitary hormone βLPH in size and structure. A tryptic peptide similar to the lipotropin tryptic peptide that contains the opiate-active methionine-enkephalin sequence could be identified in 31,000 dalton ACTH and in all the different forms of endorphin. The tryptic peptides found in phenylalanine- or tryptophan-labeled 31,000 dalton ACTH were identical to the tryptic peptides found in digests of 31,000 dalton endorphin labeled with the same amino acid. Purified pools of the different forms of ACTH and endorphin were prepared by immunoprecipitation and gel filtration. Sequential immunoprecipitation of culture medium with the ACTH antiserum and then with the endorphin antiserum (or the reverse order) indicated that both antisera precipitated the same 31,000 dalton molecule. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of phenylalanine-labeled immunoprecipitates prepared with endorphin antisera resolved three forms of endorphin with apparent molecular weights of 31,000, 11,700, and 3500 immunoprecipitates prepared with the ACTH antiserum contained four forms of ACTH with apparent molecular weights of 31,000, 23,000, 13,000 and <4500. Cultures were incubated with a 3H-labeled amino acid, and aliquots of culture medium were immunoprecipitated. Double-antibody immunoprecipitation procedures with antisera to endorphins and to corticotropin (ACTH) were used to study the biosynthesis of these peptides in a mouse pituitary tumor cell line.
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