An in vivo procedure for the selective inactivation of rat brain cerebral cortical alpha-adrenoceptors using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ).
Intraperitoneal administration of 0.8 mg/kg N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) to rats significantly reduced alpha-adrenoceptor binding in cerebral cortical membranes without affecting beta-adrenoceptor sites. A selective reduction in alpha 1-adrenoceptors was achieved by injecting yohimbine prior to EEDQ, whereas prazosin pretreatment yielded a selective reduction in alpha 2-adrenoceptor binding. Administration of EEDQ decreased norepinephrine-stimulated inositol phosphate and cyclic adenosine monophosphate (cAMP) accumulation in cerebral cortical tissue as well as the cAMP response to isoproterenol in combination with 6-fluoronorepinephrine without modifying the second messenger response to isoproterenol alone. The results suggest that, under the proper conditions, EEDQ administration can selectively diminish rat brain alpha-adrenoceptor number and function, yielding a procedure that may be useful for defining the behavioral and physiological properties of these sites.
Pilc
A
A
Institute of Pharmacology, Polish Academy of Sciences, Krakow.
Vetulani
J
J
Nomura
S
S
Enna
S J
SJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003000:Clonidine / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000031:analogs & derivatives / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D007295:Inositol Phosphates; D011804:Quinolines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D004082:Dihydroalprenolol; C000470:EEDQ; C024884:6-fluoronorepinephrine; D000242:Cyclic AMP; D007545:Isoproterenol; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin