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MECHANISM BY WHICH CYPROHEPTADINE INHIBITS INSULIN SECRETION
Author(s) -
DONATSCH P.,
LOWE D.A.,
RICHARDSON B.P.,
TAYLOR PAMELA
Publication year - 1980
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1980.tb08710.x
Subject(s) - cyproheptadine , veratridine , endocrinology , medicine , extracellular , depolarization , calcium , insulin , chemistry , tolbutamide , secretion , intracellular , pancreatic islets , ionophore , islet , biology , biochemistry , sodium , receptor , sodium channel , organic chemistry , serotonin
1 Isolated islets of Langerhans from the rat have been used in studies designed to elucidate the mechanism by which cyproheptadine inhibits insulin secretion. 2 d ‐Glucose and tolbutamide, both of which require extracellular Ca 2+ to produce insulin release, failed to evoke a secretory response from islets pretreated with cyproheptadine. Conversely veratridine, the calcium ionophore A23187 and theophylline, all of which are capable of mobilizing sufficient intracellular Ca 2+ to evoke insulin secretion in the absence of extracellular Ca 2+ , produced similar responses from cyproheptadine pretreated and control islets. 3 Cyproheptadine completely inhibited Ca 2+ uptake induced by d ‐glucose and high K + o , two agents which depolarize the islet β‐cell membrane, whilst Ca 2+ uptake elicited by removal of extracellular Na + (i.e. Na + ‐Ca 2+ counter transport) was only slightly reduced. 4 A significant increase in Na + uptake produced by veratridine was sensitive to tetrodoxin but only partially reduced by cyproheptadine. 5 These results suggest that cyproheptadine inhibits depolarization‐dependent calcium entry into pancreatic β‐cells.