The effects of guanyl-5′-yl imidodiphosphate (Gpp(NH)p) and sodium on muscarinic receptor binding in the rat brain and longitudinal muscle of the rat ileum were investigated using the specific muscarinic affinity label [3H](-) quinuclidinyl benzilate ([3H](-)QNB). When measured by competitive inhibition of [3H](-)QNB binding to homogenates of the longitudinal muscle of the ileum, the IC50′s of oxotremorine and carbachol increased by a factor of 3 in the presence of 30 μM Gpp(NH)p. In contrast Gpp(NH)p only produced small increases in agonist IC50 values when binding experiments were done on various rat brain regions. The agonist inhibition curves deviated from the law of mass action and were consistant with a two binding site model. Nonlinear regression analysis showed variation in the percentage of high affinity agonist sites in the cerebellum (68%), brainstem (68%), longitudinal muscle of the ileum (44-50%) and forebrain (21-30%). In the ileum and forebrain, the predominant effect of Gpp(NH)p on agonist binding was a reduction in the affinity of the high affinity agonist binding site. In the cerebellum and brainstem Gpp(NH)p had no effect. Furthermore, Gpp(NH)p had no significant effect on antagonist binding in any tissue. The influence of sodium (200 mM NaCl) on muscarinic receptor binding was investigated in homogenates of the forebrain and longitudinal muscle of the ileum, and a preferential reduction of agonist affinity by sodium was observed.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)