Effects of the 5-HT2C/2B receptor agonist 1-(3-chlorophenyl) piperazine on plasma glucose levels of rats.
Acute administration of the 5-HT2C/2B receptor agonist 1-(3-chlorophenyl)piperazine (mCPP, 5-10 mg/kg i.p.) induced hyperglycemia in rats. These changes were diminished in a dose-dependent manner by the 5-HT1/5-HT2 receptor antagonist methysergide and the 5-HT2A/2B/2C receptor antagonist ritanserin. In addition, mCPP-induced hyperglycemia was dose dependently diminished by the ganglionic blocker hexamethonium and was prevented by prior adrenodemedullation. Neither the 5-HT2A receptor antagonist ketanserin nor the 5-HT3/5-HT4 receptor antagonist (3-alpha-tropanyl)-1 H-indole-3-carboxylic acid ester (ICS 205-930) proved effective against mCPP-induced hyperglycemia. Lastly, administration of the 5-HT2A/2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI) increased plasma glucose levels through ketanserin- and ritanserin-sensitive processes. Our results suggest that hyperglycemia elicited by mCPP is mediated by 5-HT2C and/or 2B receptors, and in turn adrenomedullary catecholamine release, whereas that elicited by DOI involves 5-HT2A receptors.
Sugimoto
Y
Y
Department of Pharmacology, Kobe Pharmaceutical University, Japan.
Yamada
J
J
Yoshikawa
T
T
Horisaka
K
K
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism*; D018738:Hexamethonium / Q000494:pharmacology; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000662:Amphetamines; D001786:Blood Glucose; D010879:Piperazines; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D018738:Hexamethonium; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C015068:1-(3-chlorophenyl)piperazine