Functional and physical properties of chick atrial and ventricular GTP-binding proteins: relationship to muscarinic acetylcholine receptor-mediated responses.
Activation of muscarinic acetylcholine receptors in chick atria, but not ventricles, causes an increase in K+ permeability. Because of suggestions that this difference in muscarinic receptor-mediated physiological responses may be due to changes in the guanine nucleotide regulatory proteins (termed Go and Gi) associated with the receptor, we compared the functional and biochemical properties of these proteins in atria and ventricles from 8-day chick embryos. The affinity of agonist for the muscarinic receptor in either the absence or presence of guanine nucleotides was the same in membranes from atria and ventricles; similar concentrations of guanyl-5'-yl imidodiphosphate were required to regulate agonist binding in both tissues (EC50 of 2.7 X 10(-8) and 2.0 X 10(-8) M for atria and ventricles, respectively). Forskolin-stimulated adenylate cyclase activity in atria and ventricles was equally sensitive to inhibition by guanyl-5'-yl imidodiphosphate. In addition, the muscarinic agonist carbachol inhibited adenylate cyclase in ventricles with an IC50 similar to that observed in atria, although the magnitude of inhibition was slightly less in ventricles. The physical properties of the alpha subunits of the guanine nucleotide regulatory proteins were examined after covalent modification by islet activating protein. Two [32P]ADP-ribosylated polypeptides were detected by one dimensional gel electrophoresis, with molecular weights equal to those reported for Go and Gi from other tissues. Similar amounts of both proteins were found in atrial and ventricular membranes. Peptide mapping demonstrated that although the 39 and 42 kD proteins had nonidentical peptide maps, atrial and ventricular peptide maps were identical.(ABSTRACT TRUNCATED AT 250 WORDS)
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D016275:Atrial Function; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002642:Chick Embryo; D019204:GTP-Binding Proteins / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D008970:Molecular Weight; D010449:Peptide Mapping; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000502:physiology*; D016276:Ventricular Function
D008565:Membrane Proteins; D011976:Receptors, Muscarinic; D000246:Adenosine Diphosphate Ribose; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases