Differential affinities of AF-DX 116, atropine and pirenzepine for muscarinic receptors of guinea pig gastric fundus, atria and urinary bladder: might atropine distinguish among muscarinic receptor subtypes?
The pA2 values and the Schild plots of the antimuscarinic drugs AF-DX 116, atropine and pirenzepine for muscarinic receptors of isolated guinea pig gastric fundus (acid secretion) and atrial and urinary bladder preparations (contractile force) obtained from the same animals were calculated against bethanechol as the agonist. The antimuscarinic drugs concentration-dependently shifted the concentration-response curves to bethanechol to the right without any change in the maximum response. The analysis of data based on Schild plots was consistent with a simple competitive antagonism, since regression slopes did not differ significantly from unity. The pA2 values indicated a significantly higher affinity of AF-DX 116 and atropine for atrial muscarinic receptors with respect to those of the gastric mucosa or urinary bladder. By contrast, in the case of pirenzepine the pA2 values for the three tissues did not differ significantly. These results suggest that each examined tissue apparently contains homogeneous population of acetylcholine muscarinic (M2) receptors. The pA2 values found for AF-DX 116 and atropine suggest, however, that the putative M2 subtype of atrial muscarinic receptor differs from both those of the gastric fundus and those of the urinary bladder.
Del Tacca
M
M
Institute of Pharmacology, School of Medicine and Dentistry, University of Pisa, Italy.
Danesi
R
R
Blandizzi
C
C
Bernardini
M C
MC
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005748:Gastric Fundus / Q000378:metabolism / Q000648:ultrastructure*; D006168:Guinea Pigs; D006325:Heart Atria / Q000378:metabolism; D007700:Kinetics; D008297:Male; D018727:Muscarinic Antagonists; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure*; D010276:Parasympatholytics / Q000494:pharmacology*; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000145:classification*; D001743:Urinary Bladder / Q000378:metabolism / Q000648:ultrastructure*
D001626:Bethanechol Compounds; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D018723:Bethanechol; D010890:Pirenzepine; D001285:Atropine; C048593:otenzepad