The acute pharmacologic effects of serotonin on the release of insulin and glucagon in the intact rat
Jacoby, J.H.; Bryce, G.F.
Archives Internationales de Pharmacodynamie et de Therapie 235(2): 254-270
1978
ISSN/ISBN: 0003-9780 PMID: 310665 Document Number: 135625
Serotonin (5HT) (5 mg/kg-25 mg/kg; i.p.) induced a dose-related increase of plasma glucagon (IRG) (using 30K antibody) 3 to 60 min after administration to overnight fasted rats. Blood glucose (BS) also increased as early as 10 min post-injection whereas plasma insulin (IRI) increased in a non dose-related (30 min to onset) manner. Adreno-demedullation prevented the rise of BS and IRI, but not IRG. Pretreatment with reserpine (5 mg/kg; i.p.; 24 h earlier) did not prevent the actions of 5HT. Pretreatment with the .alpha.-adrenergic antagonist phentolamine (3 mg/kg-6 mg/kg; i.p.) reduced but did not prevent the subsequent rise of IRG, whereas .beta.-adrenergic blockade with propranolol (5 mg/kg-10 mg/kg; i.p.) was without effect. Phentolamine and the lower dose of propranolol (5 mg/kg) reduced the 5HT-induced hyperglycemia; whereas the higher dose (10 mg/kg) prevented the hyperglycemia. Phentolamine potentiated and propranolol prevented (5 mg/kg) or reversed (10 mg/kg) the 5HT-induced IRI rise. Pretreatment with the 5HT-antagonist, methysergide, prevented all the effects of 5HT. Precursor loading with 5HTP (an L-aromatic acid decarboxylase inhibitor) blocked the subsequent rise of IRG. The 5HT-induced changes in BS and IRI may be secondary to a release of epinephrine and/or norepinephrine, but that the effects of 5HT on the release of IRG cannot be explained solely by this mechanism.