Long-term treatment with different calcium- and calmodulin-antagonists induces changes in rat brain alpha-adrenoceptors.
1. The binding characteristics (Bmax and Kd) of the alpha-adrenoceptor radioligand [3H] WB4101 in crude membrane fraction (fraction P2) from cerebral cortex were studied after 13-day oral treatment of male Wistar rats with the Ca(2+)-antagonists nifedipine (20 mg/kg), verapamil (50 mg/kg), flunarizine (10 mg/kg) and with the calmodulin-antagonist trifluoperazine (TFP) (3 mg/kg). 2. A significant reduction of the binding sites (Bmax) for [3H] WB4101 was established after the three Ca(2+)-antagonists as well as after TFP treatment. 3. Different changes in the affinity constant (Kd) of brain adrenoceptors were observed depending on the type of the Ca2+ or CaM-antagonist used: nifedipine did not change the Kd value, verapamil and TFP decreased whereas flunarizine increased the Kd value. 4. Relationships between Ca ions and alpha-adrenoceptor functions are suggested.
Staneva-Stoytcheva
D
D
Institute of Physiology, Bulgarian Academy of Sciences, Sofia.
Dantchev
N
N
Popov
P
P
D000284:Administration, Oral; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004146:Dioxanes / Q000378:metabolism; D005444:Flunarizine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D012044:Regression Analysis; D014268:Trifluoperazine / Q000008:administration & dosage / Q000494:pharmacology*; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002147:Calmodulin; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D014268:Trifluoperazine; D014700:Verapamil; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D009543:Nifedipine; D005444:Flunarizine