Characteristics of the Dopaminergic and Noradrenergic Systems of the Pancreatic Islets

Abstract

The catecholamines norepinephrine (NE) and dopamine (DA), known inhibitors of insulin secretion, have been identified in the pancreatic islets only semiquantitatively by their histochemical fluorescence spectrum. Using collagenase digestion of golden hamster pancreas, we isolated islets and quantitated the NE and DA content with sensitive and specific radioenzymatic assays. We compared the NE and DA concentrations in islets with the median eminence and cerebral cortex of the golden hamster, tissues known to contain catecholamines. Under basal conditions, NE is in higher concentration than DA in all three tissues and is highest in the islets in a much greater concentration than is found in the median eminence. DA is present in measurable quantities in all three tissues and, in the islets, its concentration is comparable with that in the median eminence.Treatment of the hamster with a precursor of the two catecholamines, L-dopa, produced a significant accumulation of DA in the islets and median eminence over the basal values. This L-dopa-induced increase in DA was heightened in the islets and reached significantly higher than control levels in the cortex by a pretreatment of the hamster with tranylcypromine (tran), a monomine oxidase inhibitor. Pretreatment with tran alone, however, produced no change in DA over control values.The NE content of pancreatic islets was not altered by administration of L-dopa, tran, or L-dopa plus tran. The NE content of the median eminence was increased by the administration of tran. L-dopa plus tran did not result in an additional increase in the NE content of the median eminence. The administration of tran plus L-dopa (but not the administration of either agent alone) increased the NE content of the cortex over control levels. The present study suggests that inhibition of insulin secretion From the Durham Veterans after L-dopa administration is due to an increased concentration of DA rather than NE in the pancreatic islets. DIABETES 28:185-189, March 1979.T hirty years ago, Sawyer, Markee, and Hollinshead first proposed a mechanism for hormone release in the anterior pituitary that depended on catecholamines. 1 Functional studies of the activity of the catecholamine system with certain endocrinologic changes 2 and further investigations with fiuorescenceimmunocytochemical techniques localizing the catecholamine storage sites 3 have established the importance of catecholamines in regulating hormone secretion. In 1963, biogenic amines were identified in the pancreatic islets of Langerhans of different species by formaldehyde-induced fluorescence. 4 Since then, precise subcellular localization of these biogenic amines to the hormone-containing granules 5 " 7 lead directly to exciting considerations of their physiologic roie in the endocrine pancreas. Some investigators have demonstrated that exogenous dopamine and serotonin inhibit in vivo and in vitro insulin release stimulated by a variety of agents in certain species. 6>8 -9~u Other investigators have shown these two amines to stim...

Autonomic function and control of pancreatic somatostatin

“…"Blockade" by butaclamol is best explained as being due to mild alpha-adrenergic antagonism. As there are large amounts of dopamine in the pancreatic islets [12] we suggest that any cellular effects of this dopaminergic system are mediated through alpha-(or beta) adrenergic receptors [5,6].…”

Therapy of malignant hamster insulinomas with monoamine precursors

“…As serotonin binds to particulate matter the serotonin analysis was done on the total HCI homogenate. The norephinephrine [13,14], dopamine [15,16], and serotonin [17,18[ concentrations in the insulinomas were determined with previously described sensitive and specific radioassays in which a 3H-labelled methyl group is transferred from 3H-S-adenosylmethionine to the monoamine under investigation by a sernipurified enzyme. After appropriate insolation, the amount of purified radioactive derivative that was generated was determined in a liquid scintillation counter.…”

Effect of increased pancreatic islet norepinephrine, dopamine and serotonin concentration on insulin secretion in the Golden hamster

“…The protein content of the homogenate was determined with a colorimetric method [12]. The norepinephrine [8,13], dopamine [3,14], and serotonin [4,15] concentrations in the islets were determined with previously described sensitive and specific radioassays in which a 3H-labelled methyl group is transferred from 3H-S-adenosylmethionine to the monoamine under investigation by a semipurified enzyme. After appropriate isolation, the amount of purified radioactive derivative that was generated was determined in a liquid scintillation counter.…”

“…The islets of the golden hamster contain norepinephrine in adrenergic nerve plexuses, but there is no evidence histochemically of dopamine or serotonin [2]. Recent studies, however, utilizing radioenzymatic assays, demonstrate a substantial concentration of dopamine and serotonin even in the islets of the hamster [3,4]. These observations raise the possibility that intracellular monoamines may play a significant role in the regulation of insulin secretion.…”

“…The Concentration of norepinephrine, dopamine and serot0nin in the pancreatic islets was increased by adminis-0012-186X/80/0018/0341/$01. 20 tering respectively the monoamine precursors DLthreo-dihydroxyphenylserine (DOPS), L-DOPA or 5-hyroxytryptophan to normal hamsters and to hamsters who were pretreated with the monoamine oxidase inhibitor tranylcypromine [3,4,8]. The animals were sacrificed and their islets isolated.…”