Clonidine displacement from type 1 imidazoline receptor by p-aminobenzamidine, the prototype of trypsin-like serine protease inhibitors.
p-Aminobenzamidine inhibits competitively the catalytic activity of enzymes that recognize preferentially the L-arginyl side chain and related structures. Notably, p-aminobenzamidine is considered as the prototype of trypsin-like serine protease inhibitors. Furthermore, p-aminobenzamidine inhibits the catalytic activity of nitric oxide synthase type I and type II as well as copper amine oxidase. Taking into account the structural similarity between p-aminobenzamidine, agmatine (the putative endogenous ligand of the membrane type 1 imidazoline receptor (I1-R)), and N-amidino-2-hydroxypyrrolidine (the product of agmatine oxidation by copper amine oxidase), the [3H]clonidine displacement from I1-R in rat heart membranes by p-aminobenzamidine was investigated. p-Aminobenzamidine is as effective as agmatine and N-amidino-2-hydroxypyrrolidine and more effective than the antihypertensive drug clonidine to displace [3H]clonidine from I1-R. Therefore, trypsin-like serine protease inhibitors structurally related to p-aminobenzamidine should be administrated under careful control.
Pallottini
Valentina
V
Department of Biology, University Roma Tre, Viale G. Marconi 446,1-00146 Roma, Italy.
Marino
Maria
M
Ascenzi
Paolo
P
D000316:Adrenergic alpha-Agonists / Q000737:chemistry / Q000494:pharmacology; D000376:Agmatine / Q000494:pharmacology; D000818:Animals; D001550:Benzamidines / Q000494:pharmacology*; D020134:Catalytic Domain; D003000:Clonidine / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D054755:Imidazoline Receptors; D007700:Kinetics; D008024:Ligands; D008297:Male; D008956:Models, Chemical; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000737:chemistry*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D001550:Benzamidines; D054755:Imidazoline Receptors; D008024:Ligands; D011955:Receptors, Drug; D015842:Serine Proteinase Inhibitors; C410887:imidazoline I1 receptors; C006500:4-aminobenzamidine; D000376:Agmatine; D014357:Trypsin; D003000:Clonidine