Interaction of iodinated quinuclidinyl benzilate enantiomers with M3 muscarinic receptors.
We examined the interaction of 3-quinuclidinyl-4-iodobenzilate enantiomers, (RR)- and (SS)-IQNB, relatively receptor-active and -inactive, respectively, with M3-muscarinic receptors (mAChRs) in rat parotid acinar cells in vitro. This stereospecific antagonist pair has often been used for in vivo studies of mAChRs. There was a 16-fold difference in the ability of (RR)- and (SS)-IQNB to bind in vitro to mAChRs; Ki values estimated by competition with N-methylscopolamine were 5.3 and 84.2 nM, respectively. However, the ability of these antagonists to inhibit carbachol-stimulated inositol trisphosphate formation (Ki values determined by Schild analyses) was more similar, 16.3 and 47.7 nM, respectively for (RR)- and (SS)-IQNB. These data suggest that while it may be useful to employ this antagonist pair to evaluate some mAChR subtypes in vivo, it is difficult to use them in studies of M3-mAChRs.
Hiramatsu
Y
Y
Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Eckelman
W C
WC
Baum
B J
BJ
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007457:Iodine Radioisotopes; D008297:Male; D019832:N-Methylscopolamine; D011813:Quinuclidinyl Benzilate / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism; D013237:Stereoisomerism
D007457:Iodine Radioisotopes; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D011813:Quinuclidinyl Benzilate; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D019832:N-Methylscopolamine