Effects of calcium antagonists on muscarinic receptor subtypes in the rat brain.
The effects of several calcium antagonists, including nicardipine, nifedipine, verapamil, and diltiazem, on muscarinic acetylcholine antagonist binding were studied in the P2 fraction of the rat cerebral cortex using either [3H]quinuclidinyl benzilate ([3H]QNB) or [3H]pirenzipine as the radioactive ligand. (1) The potency of [3H]QNB binding inhibition was in the order nicardipine greater than verapamil greater than diltiazem greater than nifedipine. The IC50 values of nicardipine, verapamil, and diltiazem were 2.56 X 10(-6) M, 1.28 X 10(-5) M, and 6.00 X 10(-5) M, respectively. (2) The inhibition of [3H]QNB binding by nicardipine was significantly decreased in the presence of Ca ions. (3) In saturation experiments of [3H]QNB binding in the presence of nicardipine, the Kd value appeared to be significantly affected, but the Bmax value was unchanged. This indicated that nicardipine probably inhibited [3H]QNB binding allosterically. On the other hand, (4) nicardipine inhibited [3H]pirenzipine binding completely with an IC50 value of 7.87 X 10(-7) M. It was concluded that nicardipine had an inhibitory effect on M1-receptor binding.
Katayama
S
S
Third Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Kito
S
S
Miyoshi
R
R
Matsubayashi
H
H
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010890:Pirenzepine / Q000378:metabolism*; D011812:Quinuclidines / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
D002121:Calcium Channel Blockers; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate