title: 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.affiliation: Department of Anatomy and Neuroscience, Faculty of Medicine, J.J. Strossmayer University of Osijek, J.Huttlera 4, 31000 Osijek, Croatia.
authors.forename: Antonio
authors.initials: A
authors.lastname: Kokot
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, POB 916, Salata 11, 10000 Zagreb, Croatia.
authors.forename: Mirna
authors.initials: M
authors.lastname: Zlatar
authors.affiliation: Department of Pharmacology, Faculty of Medicine, J.J. Strossmayer University of Osijek, J.Huttlera 4, 31000 Osijek, Croatia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Stupnisek
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, POB 916, Salata 11, 10000 Zagreb, Croatia.
authors.forename: Domagoj
authors.initials: D
authors.lastname: Drmic
authors.affiliation: Department of Anatomy and Neuroscience, Faculty of Medicine, J.J. Strossmayer University of Osijek, J.Huttlera 4, 31000 Osijek, Croatia.
authors.forename: Radivoje
authors.initials: R
authors.lastname: Radic
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, POB 916, Salata 11, 10000 Zagreb, Croatia.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Vcev
authors.affiliation: Department of Pathology, School of Medicine, University of Zagreb, Salata 9, 10000 Zagreb, Croatia.
authors.forename: Sven
authors.initials: S
authors.lastname: Seiwerth
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, POB 916, Salata 11, 10000 Zagreb, Croatia. Electronic address: sikiric@mef.hr.
authors.forename: Predrag
authors.initials: P
authors.lastname: Sikiric
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D008540:Meiosis / Q000187:drug effects*; D009184:Mydriatics / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D011680:Pupil / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D009184:Mydriatics; D010446:Peptide Fragments; D011506:Proteins; D009569:Nitric Oxide; D001285:Atropine; C083833:BPC 157; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester
keywords: Atropine; BPC 157; Guinea pigs; Miosis; NO system; Rats