KINETIC-ANALYSIS OF RAT EXOCRINE GLAND MUSCARINIC RECEPTORS IN-VIVO

Recently we employed two enantiomers of the muscarinic antagonist quin uclidinyl iodobenzilate (IQNB), and pharmacokinetic analyses, to defin e 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 approa ch for evaluating mAChRs in three other morphologically different rat exocrine glands: the submandibular, sublingual and lacrimal glands. Th e metabolism and tissue distribution of the intravenously injected IQN B 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 distri bution as measured with the receptor-inert enantiomer (SS)-IQNB. Nonsp ecific distribution represented 45, 21 and 36% of total ligand distrib ution in submandibular, sublingual and lacrimal glands, respectively, as measured with the receptor-active enantiomer (RR)-IQNB. The rank or der of the binding potential, kinetically equivalent to B-max/K-d, for (RR)-IQNB and these mAChRs was lacrimal > sublingual > submandibular g lands (674 +/- 235 > 575 +/- 109 > 345 +/- 29). These results demonstr ate that specific mAChRs in the exocrine glands can be measured in viv o with the (RR)-IQNB enantiomer and that despite some small quantitati ve 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.