Kinetic analysis of rat exocrine gland muscarinic receptors in vivo.

Recently we employed two enantiomers of the muscarinic antagonist quinuclidinyl iodobenzilate (IQNB), and pharmacokinetic analyses, to define and quantitate nonspecific and specific binding to rat parotid gland muscarinic acetylcholine receptors (mAChRs) in vivo (Hiramatsu et al., 1993). The present studies were designed to utilize this same approach for evaluating mAChRs in three other morphologically different rat exocrine glands: the submandibular, sublingual and lacrimal glands. The metabolism and tissue distribution of the intravenously injected IQNB enantiomers were determined, and the resulting data were assessed in terms of their goodness of fit to several multicompartmental models. All three exocrine glands showed substantial nonspecific ligand distribution as measured with the receptor-inert enantiomer (SS)-IQNB. Nonspecific distribution represented 45, 21 and 36% of total ligand distribution in submandibular, sublingual and lacrimal glands, respectively, as measured with the receptor-active enantiomer (RR)-IQNB. The rank order of the binding potential, kinetically equivalent to Bmax/Kd, for (RR)-IQNB and these mAChRs was lacrimal > sublingual > submandibular glands (674 +/- 235 > 575 +/- 109 > 345 +/- 29). These results demonstrate that specific mAChRs in the exocrine glands can be measured in vivo with the (RR)-IQNB enantiomer and that despite some small quantitative differences, the distribution of (RR)- and (SS)-IQNB is similar in the three exocrine glands but is substantially different from that in brain and heart.