AJP - Gastrointestinal and Liver Physiology, Vol 264, Issue 3 541-G552, Copyright © 1993 by American Physiological Society
Kinetic analysis of rat parotid gland muscarinic receptors in vivo: comparison with brain and heart
Y. Hiramatsu, R. Kawai, R. C. Reba, T. R. Simon, B. J. Baum and R. G. Blasberg
Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
(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.
