Chronic treatment with prazosin causes a subtype-specific increase in the alpha 1-adrenoceptor density of the stressed rat cerebral cortex.
The effects of chronic treatment with prazosin and of immobilization stress on the alpha 1-adrenoceptor subtypes in rat cerebral cortex have been examined. Prazosin-treated rats were allowed free access to tap water containing two different concentrations of prazosin (16 or 156 mg L-1) for 5 weeks. The mean plasma concentrations of prazosin were 5 ng mL-1 in groups treated with a low dose and 8 or 14 ng mL-1 in those treated with a high dose. Immobilization stress (2 h day-1, 2 weeks) or chronic treatment with a low dose of prazosin caused no significant change in the affinity for [3H]prazosin or in the maximum number of alpha 1-adrenoceptor sites (Bmax). However, treatment with prazosin (low dose) combined with stress increased the density of alpha 1-adrenoceptors with low affinity for prazosin. Treatment with a high dose of prazosin increased the density of alpha 1L-adrenoceptors, irrespective of stress loading. The densities of alpha 1A- and alpha 1B-adrenoceptors with high affinity for prazosin were increased only after treatment with a high dose of prazosin in combination with stress. These results indicate that three distinct alpha 1-adrenoceptor subtypes, alpha 1A, alpha 1B and alpha 1L, might be affected differently by treatment with prazosin and by stress.
Takita
M
M
Department of Pharmacology, Fukui Medical School, Japan.
Taniguchi
T
T
Zhu
J
J
Muramatsu
I
I
D000317:Adrenergic alpha-Antagonists / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects* / Q000648:ultrastructure*; D007700:Kinetics; D008297:Male; D011224:Prazosin / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000187:drug effects* / Q000378:metabolism*; D012149:Restraint, Physical; D012680:Sensitivity and Specificity; D013312:Stress, Physiological / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium
D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D014316:Tritium; D011224:Prazosin