NO system dependence of atropine-induced mydriasis and L-NAME- and L-arginine-induced miosis: Reversal by the pentadecapeptide BPC 157 in rats and guinea pigs.

Abstract

We revealed an immediate and hours-lasting particular NO-specific parallel miotic effect of L-NAME and L-arginine in rats and guinea pigs and a stable gastric pentadecapeptide BPC 157 157-particular effect vs. that of atropine-induced mydriasis while examining the NO system role in the normal pupils responses and pupils with atropine-induced mydriasis. We also assessed the responses to BPC 157 and its possible modulation of the changes caused by L-NAME/L-arginine and atropine. We administered locally (two drops/eye) or systemically (intraperitoneally/kg) [BPC 157 (0.4µg/eye; 10µg, 10ng, 10pg/kg), L-NAME (0.1mg/eye; 5mg/kg), and L-arginine (2mg/eye; 100mg/kg) alone and combined] at 3min prior to assessment (normal pupils) or alternatively at maximal 1% atropine-induced mydriasis (30min after two drops were administered to each eye). L-NAME/L-arginine. Normal pupil. L-NAME-miosis and L-arginine-miosis shortened and attenuated each other's responses when combined (L-NAME+L-arginine) (except with guinea pigs treated locally) and were thereby NO-specific. Atropine-pupil. Both L-NAME and L-arginine counteracted atropine-induced mydriasis. With few exceptions, the atropine+L-NAME+L-arginine-animals showed a consistent shift toward the left. BPC 157. Normal pupil. Always, BPC 157 alone (both species; locally; systemically; all regimens) did not affect normal pupils. Despite specific exceptions, BPC 157 distinctively affects L-arginine-miosis (prolongation) and L-NAME-miosis (shortening). When L-arginine and L-NAME were combined (L-NAME+L-arginine+BPC 157), the effect was less pronounced. Atropine-pupil. BPC 157 alone counteracted atropine-induced mydriasis. With few exceptions (when administered with L-NAME or L-arginine or L-NAME+L-arginine), BPC 157 augments their counteracting effects. Thus, along with its l-NAME/L-arginine effects, BPC 157 participates in ocular control, potentially via NO-mediated and cholinergic mechanisms.

• Authors: Antonio Kokot, Mirna Zlatar, Mirjana Stupnisek, Domagoj Drmic, Radivoje Radic, Aleksandar Vcev, Sven Seiwerth, Predrag Sikiric
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 771 Pg. 211-9 (Jan 15 2016) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 26698393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Enzyme Inhibitors
• Mydriatics
• Peptide Fragments
• Proteins
• Nitric Oxide
• Atropine
• BPC 157
• Arginine
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Arginine (pharmacology)
• Atropine (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Guinea Pigs
• Male
• Meiosis (drug effects)
• Mydriatics (pharmacology)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide (metabolism)
• Peptide Fragments (pharmacology)
• Proteins (pharmacology)
• Pupil (drug effects)
• Rats
• Rats, Wistar