title: Effects of calcium antagonists on muscarinic receptor subtypes in the rat brain.
abstract: 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.
authors: Third Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
authors: S
authors: S
authors: Katayama
authors: S
authors: S
authors: Kito
authors: R
authors: R
authors: Miyoshi
authors: H
authors: H
authors: Matsubayashi
mesh_terms: 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
chemical_list: D002121:Calcium Channel Blockers; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate