Guanylpirenzepine distinguishes between neuronal ml and m4 muscarinic receptor subtypes.
Guanylpirenzepine, a polar, non-quaternary analog of pirenzepine, exhibited a novel binding behavior in rat brain regions: in competition binding experiments against [3H]pirenzepine labeling the M1 receptor in membranes from cerebral cortex, hippocampus and striatum, the compound, differently from pirenzepine, displayed heterogeneous binding curves. Computer assisted analysis of these curves, evidenced the existence of two populations of binding sites: a large proportion (84-89%) of high affinity receptors (KH = 64-92 nM) and a remainder with very low affinity (KL = 19-28 microM). Like pirenzepine, guanylpirenzepine showed low affinity for the glandular M3 and the cardiac M2 receptors when [3H]N-methylscopolamine was used to label the receptors in membranes from these two tissues; affinity values for guanylpirenzepine were 1336 and 5790 nM respectively, vs 323 and 683 nM for pirenzepine. We conclude that guanylpirenzepine is able to discriminate between m1 and m4 receptor subtypes and may represent a new tool for deeper studies on muscarinic receptors classification.
Monferini
E
E
Department of Biochemistry, Istituto De Angeli S.p.A., Milan, Italy.
Cereda
E
E
Ladinsky
H
H
Donetti
A
A
Giraldo
E
E
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000648:ultrastructure; D009474:Neurons / Q000648:ultrastructure*; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000145:classification* / Q000378:metabolism / Q000502:physiology; D013363:Submandibular Gland / Q000648:ultrastructure; D013552:Swine; D014316:Tritium
D011976:Receptors, Muscarinic; D014316:Tritium; C066403:guanylpirenzepine; D010890:Pirenzepine