title: Kinetic analysis of rat parotid gland muscarinic receptors in vivo: comparison with brain and heart.
abstract: (RR)- and (SS)-quinuclidinyl iodobenzilate enantiomers [(RR)- and (SS)-IQNB, active and inert, respectively] have been synthesized for quantitative evaluation of muscarinic acetylcholine receptor (mAChR) binding. Pharmacokinetic approaches have not been used previously to assess in vivo IQNB binding in nonexcitable tissues. We have applied this method to examine mAChRs in rat parotid gland in comparison to those in brain and heart. Short-term infusion studies in vivo showed that the "instantaneous" reversible binding of (RR)- and (SS)-IQNB was high in the parotid (greater nonspecific binding potential), intermediate in the heart, and lowest in cortex and cerebellum. Long-term bolus injection experiments showed that the parotid gland mAChRs possessed a binding potential for receptor specific sites (380), which was intermediate between that of parietal cortex (930) and cerebellum (10) and greater than that of heart (165). In vitro binding to plasma membranes was generally consistent with the in vivo findings. In aggregate, these studies show that mAChRs can be evaluated in vivo in a nonexcitable tissue with the use of stereospecific ligands and a pharmacokinetic approach. The data suggest that IQNB, a mAChR antagonist, can identify characteristics of specific binding sites, which may reflect tissue differences.
authors.affiliation: Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Y
authors.initials: Y
authors.lastname: Hiramatsu
authors.forename: R
authors.initials: R
authors.lastname: Kawai
authors.forename: R C
authors.initials: RC
authors.lastname: Reba
authors.forename: T R
authors.initials: TR
authors.lastname: Simon
authors.forename: B J
authors.initials: BJ
authors.lastname: Baum
authors.forename: R G
authors.initials: RG
authors.lastname: Blasberg
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D001923:Brain Chemistry; D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D007267:Injections; D008297:Male; D009206:Myocardium / Q000737:chemistry* / Q000166:cytology / Q000648:ultrastructure; D010306:Parotid Gland / Q000737:chemistry* / Q000166:cytology / Q000648:ultrastructure; D011813:Quinuclidinyl Benzilate / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000032:analysis* / Q000378:metabolism; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate