Mechanisms underlying the effects of 5-hydroxytryptamine and 5-hydroxytryptophan in pancreatic islets. A proposed role for L-aromatic amino acid decarboxylase.
Microdissected pancreatic islets of noninbred ob/ob mice were used in studies of 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP) effects on insulin release. The potentiating effect of 4 mM L-5-HTP on glucose-induced insulin release was inhibited by the decarboxylase inhibitors benserazide (100 microM), alpha-monofluoromethyldopa (10 or 100 microM), carbidopa (50 or 500 microM), and NSD 1015 (5 or 50 microM). Activation of L-aromatic amino acid decarboxylase by DL-m-tyrosine (4 mM) or DL-o-tyrosine (4 mM) potentiated glucose-induced insulin release, whereas L-dopa (4 mM) inhibited it. Glucose oxidation was unaffected by L-5-HTP but slightly stimulated by 5-HT. Glucose-induced efflux of 33Pi was reduced by 5-HT but not affected by 5-HTP. These results are compatible with the ideas that 5-HT inhibits glucose-induced insulin release by affecting early steps in the beta-cell stimulus-secretion coupling and that 5-HTP-potentiation of insulin release is probably mediated by the decarboxylase activity but is independent of the 5-HT formed.
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects*; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*
D007328:Insulin; D012701:Serotonin; D006916:5-Hydroxytryptophan; D001142:Aromatic-L-Amino-Acid Decarboxylases; D002118:Calcium