Phosphoramidon potentiates mammalian tachykinin-induced biting, licking and scratching behaviour in mice.
The effects of peptidase inhibitors were examined upon behavioural responses including scratch, bite and lick produced by intrathecal (IT) injection of substance P (SP) and neurokinin A (NK A) in mice. Phosphoramidon (0.002-2.0 nmol), an endopeptidase-24.11 inhibitor, simultaneously injected with SP or NK A, remarkably enhanced and prolonged SP- or NK A-induced behavioural response in a dose-dependent manner. The behavioural response to SP was significantly increased by 2.0 nmol of bestatin, an aminopeptidase inhibitor, but not by 1.0 nmol. Captopril, an angiotensin-converting enzyme inhibitor, was without effect on both tachykinin-induced responses. When phosphoramidon was injected together with bestatin and captopril which have no significant effect alone, SP- or NK A-induced behavioral response was significantly increased. These data suggest that endopeptidase-24.11 may be an important enzyme responsible for terminating of SP- or NK A-induced behavioral response at the spinal cord level.
Sakurada
T
T
Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.
Tan-No
K
K
Yamada
T
T
Sakurada
S
S
Kisara
K
K
D000374:Aggression / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006020:Glycopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015288:Neurokinin A / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000008:administration & dosage / Q000494:pharmacology*
D006020:Glycopeptides; D015320:Tachykinins; D013373:Substance P; D015288:Neurokinin A; D002216:Captopril; D007930:Leucine; C012211:ubenimex; C008890:phosphoramidon