The acute pharmacologic effects of serotonin on the release of insulin and glucagon in the intact rat.
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 hr 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 (5 mg/kg-50 mg/kg; i.p.) also resulted in a dose-related increase of IRG and a slight increase of IRI. Blockade of the conversion of 5HTP to 5HT with Ro-4-4602 (an L-aromatic acid decarboxylase inhibitor) blocked the subsequent rise of IRG. These results suggest that 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.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000313:Adrenal Medulla / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D012701:Serotonin; D012110:Reserpine; D005934:Glucagon; D011433:Propranolol; D006916:5-Hydroxytryptophan; D008784:Methysergide; D010646:Phentolamine