Central 5-hydroxytryptamine2 receptors are involved in the adrenal catecholamine-releasing and hyperglycemic effects of the 5-hydroxytryptamine indirect agonist d-fenfluramine in the conscious rat.
Stimulation of either the 5-hydroxytryptamine (5-HT)1A, the 5-HT1C or the 5-HT2 receptor subtype triggers adrenal catecholamine release and hyperglycemia. Nonetheless, the identity of the serotonergic receptors that mediate the effects of 5-HT release upon the sympathoadrenal system (and on plasma glucose) is still unknown. Thus, we have examined the effects of the 5-HT uptake inhibitor and releaser d-fenfluramine (d-Fen) on plasma epinephrine (EPI), norepinephrine (NE) and glucose levels in conscious rats. Acute administration of d-Fen (1-8 mg/kg i.v.) promoted early increases in plasma EPI and glucose levels, whereas increases in plasma NE levels were less marked. The effects of a 4-mg/kg dose of d-Fen were then evaluated. Prior adrenalectomy prevented d-Fen-induced hyperglycemia but not d-Fen-induced increases in plasma NE levels. Pretreatment (15 min beforehand) with either the 5-HT1C/5-HT2 receptor antagonist LY 53857 (0.3 mg/kg i.v.) or the 5-HT2 receptor/alpha-1 adrenoceptor antagonist ketanserin (0.3 mg/kg i.v.) markedly diminished the EPI-releasing effect of d-Fen. Pretreatment with the 5-HT1C receptor agonist/5-HT2 receptor antagonist m-chlorophenylpiperazine (1 mg/kg i.v.) tended to decrease the EPI-releasing effect of d-Fen, whereas that with the peripheral 5-HT1C/5-HT2 receptor antagonist BW 501C67 (0.5 mg/kg i.v.) did not alter the EPI-releasing effect of d-Fen. In addition, pretreatment with either LY 53857 or ketanserin prevented the hyperglycemic effect of d-Fen.(ABSTRACT TRUNCATED AT 250 WORDS)
Chaouloff
F
F
Department of Medicine, Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts.
Gunn
S H
SH
Young
J B
JB
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000315:Adrenalectomy; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D002395:Catecholamines / Q000097:blood*; D005277:Fenfluramine / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology
D000662:Amphetamines; D001786:Blood Glucose; D002395:Catecholamines; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D005277:Fenfluramine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C015068:1-(3-chlorophenyl)piperazine