Influence of long-term treatment with the Ca2(+)-antagonists nifedipine, verapamil, flunarizine and with the calmodulin antagonist trifluoperazine on beta-adrenoceptors in rat cerebral cortex.
1. The binding of [3H] dihydroalprenolol ((3H]DHA) to beta-adrenoceptors in cerebral cortex membranes (fraction P2) was studied after 13-day oral treatment of male Wistar rats with the Ca2(+)-antagonists nifedipine (20 mg/kg), verapamil (50 mg/kg), flunarizine (10 mg/kg) and with the calmodulin (CaM)-antagonist trifluoperazine (TFP) (3 mg/kg). 2. A significant reduction in the number (Bmax) of binding sites for [3H]DHA was established after the 3 Ca2(+)-antagonists as well as after TFP. 3. No changes in the affinity values (Kd) [3H]DHA binding were found in all treated groups. 4. The fluidity characteristics of the cerebral cortex membranes in nifedipine- and flunarizine-treated rats did not differ from those in controls. 5. Based on these results, we concluded that long-term treatment with Ca2(+)- and calmodulin-antagonists might induce changes in the central adrenergic mechanisms.
Staneva-Stoytcheva
D
D
Institute of Physiology, Bulgarian Academy of Sciences, Sofia.
Popova
J
J
Mutafova-Yambolieva
V
V
Alov
P
P
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004082:Dihydroalprenolol; D005444:Flunarizine / Q000494:pharmacology; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014268:Trifluoperazine / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002147:Calmodulin; D011943:Receptors, Adrenergic, beta; D014268:Trifluoperazine; D004082:Dihydroalprenolol; D014700:Verapamil; D009543:Nifedipine; D005444:Flunarizine