Aprophit: an irreversible antagonist for muscarinic receptors.
The development of selective irreversible ligands has proven to be an invaluable technique for the isolation, purification and characterization of many receptor proteins. An isothiocyanato-derivative of the muscarinic antagonist aprophen was synthesized and evaluated as a potential irreversible ligand for muscarinic receptors. This compound (aprophit) displaced [3H]N-methylscopolamine binding from rat cerebral cortex with a Ki of 3.1 x 10(-7) M. The inhibition was concentration-dependent and could not be reversed by extensive washing. Aprophit inhibited the acetylcholine-stimulated release of catecholamines from isolated, perfused guinea pig adrenal glands in a concentration-dependent manner. This inhibition was not reversed by perfusing the tissue with Locke's solution and was not due to a non-selective acylation by the isothiocyanate function. The data suggest that aprophit is selectively acylating muscarinic receptor proteins and thus may be useful in their further characterization.
Newman
A H
AH
Department of Applied Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Covington
J
J
Oleshansky
M
M
Jackson
B W
BW
Weissman
B A
BA
Leader
H
H
Chiang
P K
PK
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male; D019832:N-Methylscopolamine; D010276:Parasympatholytics / Q000494:pharmacology*; D010666:Phenylpropionates / Q000494:pharmacology*; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012602:Scopolamine Derivatives / Q000378:metabolism; D013861:Thiocyanates / Q000494:pharmacology*
D002395:Catecholamines; D010276:Parasympatholytics; D010666:Phenylpropionates; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D013861:Thiocyanates; C065764:aprophit; D010890:Pirenzepine; D001285:Atropine; C006615:aprofen; D019832:N-Methylscopolamine