The muscarinic receptor of chick embryo cells: correlation between ligand binding and calcium mobilization

J Cell Biol. 1985 Apr;100(4):1073-81. doi: 10.1083/jcb.100.4.1073.

Abstract

In this report we characterize muscarinic cholinergic receptor on embryonic cells. We established dose-response curves by fluorometric measurement of Ca2+ mobilization in cell suspensions of whole chick embryos stage 23/24. Ca2+ mobilization was quantitated by standardization of chlorotetracycline (CTC) fluorescence changes after stimulation with muscarinic agonists. We determined ED50 values for the agonists acetylcholine and carbachol as 3.4 X 10(-6) and 2.7 X 10(-5) M, respectively. Pilocarpine and oxotremorine were found to act as reversible competitive antagonists with inhibition constants (Kl) of 5.0 X 10(-6) and 1.4 X 10(-6) M, respectively. Bethanechol, which induced only 23% of the maximal effect obtained by acetylcholine, was a partial agonist with an ED50 of 4.8 X 10(-4) M. Its antagonistic component is expressed by an inhibition constant of 1.9 X 10(-4) M. In parallel, binding studies were performed in a competition assay with [3H]-quinuclidinylbenzilate. For the agonists acetylcholine and carbachol, binding parameters were best fitted by a "two binding-sites model." Comparison with dose-response curves indicated that Ca2+ mobilization was triggered via the high-affinity binding site. The inhibition constants of antagonists derived from the shift of dose-response curves corresponded to the fitted KD values of the binding studies when a "one binding-site model" was applied. Combination of dose-response and binding data showed close proportionality between receptor occupancy and calcium mobilization. No spare receptors were present.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Bethanechol
  • Bethanechol Compounds / pharmacology
  • Binding, Competitive
  • Calcium / metabolism*
  • Carbachol / pharmacology
  • Chick Embryo
  • Dose-Response Relationship, Drug
  • Oxotremorine / pharmacology
  • Pilocarpine / pharmacology
  • Quinuclidinyl Benzilate / metabolism
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / physiology*
  • Spectrometry, Fluorescence

Substances

  • Bethanechol Compounds
  • Receptors, Muscarinic
  • Bethanechol
  • Pilocarpine
  • Oxotremorine
  • Quinuclidinyl Benzilate
  • Carbachol
  • Acetylcholine
  • Calcium