Desipramine treatment differently down-regulates beta-adrenoceptors of freshly isolated neurons and astrocytes.
Eight days' desipramine administration (16 mg/kg per day i.p.) to rats resulted in a significant decrease in the density of beta-adrenoceptors in neuronal and astroglial cells from rat forebrain and cerebellum without modification of their corresponding affinity. beta-Adrenoceptor subtypes, beta 1 and beta 2, which coexist in neurons and astrocytes, are differently distributed in the brain and differently modified by desipramine administration which down-regulates beta 1-adrenoceptor in forebrain neurons and astrocytes and beta 2-adrenoceptor in cerebellum neurons. This down-regulation affects the predominant subtype, beta 1 or beta 2, of the relevant structure. Astroglial and neuronal beta-adrenoceptors are differently coupled to G-proteins. Only neuronal cells contain the high-affinity conformational state of the beta-adrenoceptors which is sensitive to GTP. The percentage of neuronal receptors in the high-affinity state differs according to brain area. Desipramine treatment decreases the neuronal density of both cerebellar high- and low-affinity sites and only the forebrain high-affinity site. The desipramine effects are thus subtype-dependent and differ between the two brain areas selected.
Sapena
R
R
Département de Pharmacologie, Faculté de Médecine de Paris XII, Créteil, France.
Morin
D
D
Zini
R
R
Morin
C
C
Tillement
J P
JP
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D007093:Imidazoles / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011412:Propanolamines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000145:classification / Q000187:drug effects* / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C049763:CGP 20712A; C033394:CGP 12177; D003891:Desipramine