EVIDENCE FOR THE PRESENCE OF SEROTONERGIC NERVE FIBERS IN THE FETAL AND ADULT MAMMALIAN PANCREAS.
Item
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Title
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EVIDENCE FOR THE PRESENCE OF SEROTONERGIC NERVE FIBERS IN THE FETAL AND ADULT MAMMALIAN PANCREAS.
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Identifier
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AAI8203293
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identifier
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8203293
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Creator
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KOEVARY, STEVEN B.
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Contributor
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Robert C. McEvoy
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Date
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1981
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Anatomy
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Abstract
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No evidence for the existence of serotonergic neurons in the mammalian pancreas has been previously reported. This question was examined by measuring the ability of rat pancreatic fragments to accumulate ('3)H-5HT at low concentrations. This technique has been used widely for the demonstration of brain and gut serotonergic nerves. After incubating pancreatic tissue ('3)H-5HT was demonstrated to be taken up avidly. Maximal uptake occurrred after 15 minutes of incubation. The uptake was demonstrated to be saturable, and was reduced by increasing concentrations of unlabelled serotonin. The apparent uptake constant for this saturable uptake was 8.75 x 10('-7)M, and the Vmax was 873 pmoles/gram. Adrenergic nerves were an unlikely site for uptake of ('3)H-5HT, since incubation in the presence of excess norepinephrine did not reduce the uptake. In addition, the serotonin receptor blocker, metergoline, did not affect the uptake, suggesting a lack of a binding component in the uptake. However, in vitro incubation of pancreatic fragments with parachloroamphetamine and/or 5,7-dihydroxytryptamine, both serotonin neurotoxic drugs, completely obliterated the specific uptake.;The saturable and specific uptake of serotonin was found to be uniform throughout the pancreas, and no sexual differences could be demonstrated. Rabbit, hamster and monkey pancreatic fragments were also demonstrated to specifically accumulate ('3)H-5HT. Radioautography on sections of the tissue slices after uptake revealed the specific uptake sites as dense aggregates of silver grains in the connective tissue spaces of the exocrine and endocrine pancreas, as well as in the walls of the pancreatic vasculature, all areas known to be traversed by nerve fibers. Such a localization of grains suggests a possible innervation of these structures by serotonergic nerves.;Fenfluramine, a drug which has been demonstrated to release brain serotonin, significantly augmented the pancreatic release of newly uptaken ('3)H-5HT. Veratridine, a drug which causes nerve depolarization, similarly stimulated the release of ('3)H-5HT.;Fetal rat pancreata (18, 20 and 22 days) were also demonstrated to specifically take up serotonin. Radioautography revealed similar uptake sites as in the adult, except that in addition, cells, possibly representing primitive neuronal perikarya, were demonstrated to be heavily labelled. This suggested a possible intrapancreatic location for the cell bodies of these nerves. The preservation of the specific serotonin uptake in 18 day fetal tissue after 4 days in organ culture, substantiated this view.;The presence of serotonergic nerve fibers suggested that the pancreas may contain the biosynthetic enzymes necessary for the synthesis of neurotransmitter. Indeed, rat pancreatic homogenates revealed tryptophan hydroxylase activity. Tryptophan hydroxylase is the rate limiting enzyme in serotonin synthesis from tryptophan.;Demonstration of serotonin containing nerve fibers in the rat pancreas by specific immunocytochemical techniques was attempted. Only pancreatic mast cells were stained. Islet cells could be stained, but only after prior administration of 5-hydroxytryptophan. The immunocytochemical staining of gut enterochromaffin cells for serotonin served as a positive control. Gut serotonergic nerve fibers were also unstained.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
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Program
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Biomedical Sciences
