[Effects of tricyclic antidepressant drugs on receptor binding sites and Ca2+ binding to sarcoplasmic reticulum in rat heart].
The effects of tricyclic antidepressant drugs on cardiac receptor binding sites and Ca2+ binding to cardiac sarcoplasmic reticulum were investigated in rats. 1) Quinupramine was found to possess higher affinity for muscarinic cholinergic receptor binding sites in brain and heart, compared with imipramine. 2) Repeated quinupramine treatment induced a significant increase in the Bmax value in cardiac muscarinic cholinergic receptors. 3) In imipramine treated heart, isoproterenol-induced stimulation of ornithine decarboxylase activity was significantly decreased compared with that in the vehicle control. 4) Repeated quinupramine and imipramine treatment caused a significant reduction of Bmax of 45Ca2+ binding in cardiac sarcoplasmic reticulum fractions. 5) After single quinupramine treatment, its concentrations in heart were higher than those in brain and plasma. 6) After the repeated quinupramine treatment, its concentration in heart was 2.4 times higher than that after single treatment. These results demonstrate that repeated tricyclic antidepressant drug treatment caused a functional impairment in Ca2+ binding sites of cardiac sarcoplasmic reticulum and adaptive changes of receptor binding sites.
Sakamoto
H
H
Department of Pharmacology, Kyoto Pharmaceutical University, Japan.
Yokoyama
N
N
Nishimoto
T
T
Kohno
S
S
Ohata
K
K
Murai
K
K
Tatsumi
H
H
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D003984:Dibenzazepines / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011812:Quinuclidines / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D000929:Antidepressive Agents, Tricyclic; D003984:Dibenzazepines; D011812:Quinuclidines; C028338:quinupramine; D002118:Calcium