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.
Edwards
E
E
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore 21201-1180, USA.
Hampton
E
E
Ashby
C R
CR
Zhang
J
J
Wang
R Y
RY
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