Recombinant enkephalinase effectively inhibits substance P-induced miosis in the rabbit eye cup model.
Enkephalinase (EC 3.4.24.11) is a naturally occurring, membrane-bound peptidase that degrades substance P in vivo and in vitro. Addition of this neutral endopeptidase to a rabbit eye cup model partially inhibits substance P-induced contraction of the iris sphincter muscle. Inactivation of substance P is reversed by thiorphan, a specific inhibitor of enkephalinase. These results show that enkephalinase degradation of substance P produces metabolites that are physiologically inactive in iris contraction. We also observed that atropine acts synergistically with enkephalinase to completely abolish substance P-induced iris contraction suggesting that the action of substance P on the iris contains an acetylcholine-stimulatory effect which is not lost by enkephalinase treatment.
Ophthalmology Research Laboratory, Sharp Cabrillo Hospital, San Diego, CA.
J A
JA
Anderson
E
E
Hernandez
E
E
Duzman
B
B
Malfroy
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007498:Iris / Q000187:drug effects*; D015877:Miosis / Q000139:chemically induced*; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins; D013373:Substance P / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015244:Thiorphan / Q000494:pharmacology
D011994:Recombinant Proteins; D013373:Substance P; D001285:Atropine; D015244:Thiorphan; D015260:Neprilysin