The long-term treatment with the Ca(2+)-antagonists nifedipine, verapamil, flunarizine and with the calmodulin antagonist trifluoperazine decreases the activity of 5-HT1 receptors in rat cerebral cortex and hippocampus.
1. The binding activity of 5-HT1 receptors was studied in membrane fractions from the cerebral cortex and hippocampus of male Wistar rats treated orally for 13 days with the Ca(2+)-antagonists nifedipine (20 mg/kg), verapamil (50 mg/kg) and flunarizine (10 mg/kg) and with the calmodulin antagonist trifluoperazine (3 mg/kg). 2. The binding capacity and affinity of the 5-HT1 receptors in the cerebral cortex were significantly decreased after the treatment with the Ca(2+)-antagonists nifedipine, verapamil and flunarizine. The dissociation constant (Kd) was increased after the treatment with the calmodulin antagonist trifluoperazine. 3. In the hippocampus the 5-HT1 receptor affinity and number of binding sites were significantly reduced after the treatment with all four antagonists tested--nifedipine, verapamil, flunarizine and trifluoperazine, the Kd value being increased insignificantly after the flunarizine treatment. 4. The results obtained afford the suggestion that the reduction of 5-HT1 receptor activity is at least one of the results of the well known Ca(2+)-ions mediated automodulation of 5-HT release. The data confirm the view about the great importance of Ca(2+)-ions for the regulation of membrane neurotransmitter receptor activities.
Popova
J
J
Institute of Endocrinology and Gerontology, Bulgarian Medical Academy, Sofia.
Staneva-Stoytcheva
D
D
Ivanova
E
E
Tosheva
T
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005444:Flunarizine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists; D014268:Trifluoperazine / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002147:Calmodulin; D012702:Serotonin Antagonists; D014268:Trifluoperazine; D014700:Verapamil; D009543:Nifedipine; D005444:Flunarizine