Evidence that 5-HT1A receptors are involved in the adrenaline-releasing effects of 8-OH-DPAT in the conscious rat.
8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) is a 5-HT1A receptor-selective agonist that has recently been reported to trigger adrenal catecholamine release and hyperglycemia. The aim of this study was to analyze in the conscious rat whether the 5-HT1A receptor subtype is involved in these effects. 8-OH-DPAT (0.1-1 mg/kg, i.v.) evoked dose-dependent increases in plasma adrenaline and glucose concentrations. Increases in plasma adrenaline levels peaked 5 min after administration of 8-OH-DPAT; in contrast, plasma glucose levels rose throughout the 20 min period of analysis. Prior administration of (-)pindolol, a beta-adrenoceptor antagonist that blocks 5-HT1A receptors, markedly diminished the rise in plasma adrenaline levels and abolished the hyperglycemia triggered by 8-OH-DPAT. On the other hand, neither the selective beta 1-adrenoceptor antagonist, betaxolol, the selective beta 2-adrenoceptor antagonist, ICI 118.551, nor the 5-HT2 receptor antagonist, ketanserin, affected 8-OH-DPAT-induced increases in plasma adrenaline levels. In addition, except for ICI 118.551 pretreatment, which delayed the hyperglycemic effect of 8-OH-DPAT, none of these antagonists affected the rise in glycaemia evoked by 8-OH-DPAT. The data suggest that the adrenaline-releasing and a major part of the hyperglycemic effects of 8-OH-DPAT are mediated by activation of 5-HT1A receptors.
Chaouloff
F
F
Laboratoire de Pharmacologie, INSERM U7, CHU Necker-E. M., Paris, France.
Baudrie
V
V
Laude
D
D
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015784:Betaxolol / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D004837:Epinephrine / Q000097:blood / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D009281:Naphthalenes; D011412:Propanolamines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C026777:ICI 118551; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D015784:Betaxolol; D004837:Epinephrine