Two distinct, divalent cation-sensitive, antagonist binding states of heart muscarinic receptors: differential modulation by guanine nucleotide

General Pharmacology
P V SulakheN T Phan

Abstract

1. The binding of [3H]quinuclidinylbenzilate (QNB), a muscarinic antagonist, to cardiac muscarinic receptors was investigated in two subcellular fractions (washed particles and microsomes) isolated from rat heart atria and ventricles. 2. 5'-guanylylimidodiphosphate (Gpp(NH)p, 0.1 mM), increased (2-3-fold) the binding to washed particles, but not to microsomes, whereas Mg2+ (1-20 mM) increased (up to 5-fold) the binding to microsomes, but not to washed particles. Gpp(NH)p modestly increased the affinity while Mg2+ decreased the affinity towards the radiolabelled antagonist. 3. Treatment with N-ethylmaleimide (NEM, 2 mM) increased the antagonist binding to either fraction. The stimulatory effect of Gpp(NH)p was not evident while that of Mg2+ survived in the NEM-treated fractions. 4. The treatment of fractions with divalent cations chelators (EDTA, EGTA; 10 mM) augmented the stimulatory effect of Mg2+ on [3H]QNB binding to microsomes while that of Gpp(NH)p on the washed particle [3H]QNB binding was decreased. Such treatment further revealed an inhibitory action (about 40%) of Mg2+ on the washed particle binding.

References

Nov 1, 1979·Naunyn-Schmiedeberg's Archives of Pharmacology·J W Wei, P V Sulakhe
Jan 1, 1984·Nihon rinsho. Japanese journal of clinical medicine·S KishimotoA Miyoshi
Oct 14, 1983·European Journal of Pharmacology·E C HulmeJ M Stockton
Jul 16, 1982·Biochemical and Biophysical Research Communications·M M Hosey
Mar 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·E BurgisserR J Lefkowitz
Jan 29, 1982·Biochemical and Biophysical Research Communications·A SastreM M Rusher
Jul 17, 1981·European Journal of Pharmacology·E C HulmeA S Burgen

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Citations

Jan 1, 1991·General Pharmacology·P V SulakheN T Phan
Jan 1, 1992·Critical Reviews in Biochemistry and Molecular Biology·J GergelyE Rajnavölgyi
May 1, 1996·Immunopharmacology and Immunotoxicology·R S WonderlingE P Mayer

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