The possible existence of two GTP-regulated processes in cardiac muscarinic receptors from computer analysis

• Published in: Japanese Journal of Pharmacology 1986, Vol.40 (suppl), p.184-184
• Main Authors: Mizushima, Atsushi, Uchida, Shuji, Zhou, Xiao-Ming, Kagiya, Toshifumi, Yoshida, Hiroshi
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)59298-8

It is well known that there exist three agonist binding sites in muscarinic receptors with different affinities (SH, H, L). Guanine nucleotide decreases the number of SH and increases that of L. Sulfhydryl reagent decreases the number of L and increases that of SH. This phenomenon involved possible two explanations; 1) SH and L have sensitivity to those reagents, and interconvertible, while H does not (SH-L and H). 2) All three sites have sensitivities to those reagents, and interconvertible each other (SH-H and H-L). We examined these two possibilities. As PrBCM alkylates muscarinic receptor with single affinity, treatment of guinea-pig cardiac membrane with both 50nM PrBCM and 500 μM carbachol(as a protector) could selectively deprive of low affinity agonist binding sites in muscarinic receptor. In such preparations, guanine nucleotide decreases SH and augments H. Sulfhydryl reagent decreases H and increases SH. These results suggested the existence of interconversion between SH and H and involvement of at least two different GTP regulated processes in cardiac muscarinic receptors, suporting the second possibility described above.