Inhibitory effects of the 5-HT(1A) receptor agonist buspirone on stress-induced hyperglycemia in mice: involvement of insulin and a buspirone metabolite, 1-(2-pyrimidinyl)piperazine (1-PP).
Effects of serotonergic anxiolytic buspirone on immobilization-induced hyperglycemia were studied in mice. Stress elicited hyperglycemia in mice. Pretreatment with buspirone significantly reduced immobilization-induced hyperglycemia. Buspirone increased serum insulin levels in both non- and stressed mice. The major metabolite of buspirone, 1-(2-pyrimidinyl)piperazine (1-PP) also increased and this further inhibited immobilization-induced hyperglycemia, since 1-PP increased serum insulin levels in both non-stressed and stressed mice, similar to the increases induced by buspirone. These results suggest that buspirone can reduce stress-induced hyperglycemia by facilitating insulin release. Moreover, 1-PP, a metabolite of buspirone may participate in the effects of buspirone. Since 1-PP is an antagonist of alpha(2) receptors, alpha(2) receptors may be related to effects of 1-PP.
Sugimoto
Yumi
Y
Department of Pharmacology, Kobe Pharmaceutical University, Japan. yumisugi@kobepharma-u.ac.jp
Takashima
Nozomu
N
Noma
Toshiko
T
Yamada
Jun
J
D000818:Animals; D002065:Buspirone / Q000031:analogs & derivatives / Q000494:pharmacology*; D006943:Hyperglycemia / Q000188:drug therapy* / Q000209:etiology; D007328:Insulin / Q000097:blood*; D008297:Male; D051379:Mice; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013312:Stress, Physiological / Q000097:blood*
D007328:Insulin; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; C037921:1-(2-pyrimidinyl)piperazine; D002065:Buspirone