5-HT3-like receptors in the rat medial prefrontal cortex: further pharmacological characterization.
The aim of the study was to further characterize the pharmacological properties of 5-hydroxytryptamine (5-HT)3-like receptors in the rat medial prefrontal cortex (mPFC) using combinations of biochemical and electrophysiological approaches. Phenylbiguanide (PBG) and three chlorinated derivatives, ortho-chloro-PBG (oCPBG), meta-chloro-PBG (mCPBG) and para-chloro-PBG (pCPBG), dose-dependently stimulated phosphoionositide (PI) turnover in fronto-cingulate cortical slices. All three chloro-isomers of PBG were equipotent in stimulating PI turnover. SR 57227A ((4-amino)-(6-chloro-2-pyridyl) L-piperidine hydrochloride, a novel compound with high affinity and selectivity for peripheral and central 5-HT3 receptors) dose-dependently stimulated PI turnover in fronto-cingulate cortical slices. The rank order of potency of all the 5-HT3 receptor agonists tested in the PI assay as compared to 5-HT was: 5-HT > 2-Me-5-HT > SR57227A > PBG = mCPBG = oCPBG = mCPBG. 5-HT and 5-HT receptor agonists depressed the firing rate of both spontaneously active and glutamate-activated quiescent mPFC cells in a current (dose)-dependent fashion. The rank order of effectiveness of these compounds was: 5-HT > SR57227A = 2-Me-5-HT = mCPBG = oCPBG = pCPBG = PBG. Unlike its action on the 5-HT3 receptors in the periphery or cultured cell lines, D-tubocurarine chloride appears to be non-specific in blocking the depressant action of 2-Me-5-HT, gamma-aminobutyric acid and dopamine. Our results combined support the view that the pharmacological properties of 5-HT3-like receptors in the mPFC are not identical to those located in peripheral tissues and in cultured cell lines.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore 21201-1180, USA.
E
E
Edwards
E
E
Hampton
C R
CR
Ashby
J
J
Zhang
R Y
RY
Wang
D000818:Animals; D001645:Biguanides / Q000737:chemistry / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology; D005625:Frontal Lobe / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D006868:Hydrolysis; D007211:Indoles / Q000494:pharmacology; D007536:Isomerism; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000737:chemistry* / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000032:analysis*; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014403:Tubocurarine / Q000494:pharmacology
D001645:Biguanides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007211:Indoles; D018733:Nicotinic Antagonists; D010716:Phosphatidylinositols; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C075685:BRL 46470; D016713:Ritanserin; D012701:Serotonin; D018698:Glutamic Acid; C045918:2-methyl-5-HT; C083009:4-amino-1-(6-chloro-2-pyridyl)piperidine hydrochloride; C008846:phenyl biguanide; D014403:Tubocurarine