The mechanism of peptidergic miosis. I. The structural basis of miotic potency among biologically active polypeptides.
The miotic potency of eleven naturally occurring polypeptides and poly-DL-alanine was tested on the isolated anterior segment of hooded rat and golden hamster eyes in order to gain information on the chemical nature of the peptides or classes of peptides which may be regarded as possible mediators of the miotic response of the mammalian eye to chemical irritants or mechanical or surgical trauma. Substance P, P-octapeptide, physalaemin and eledoisin, and eledoisin related peptide were found to be potent miotics on these preparations, yielding ED50 values in the range of 8 to 95 nM and complete pupillary constriction in the range of 100 to 1000 nM. This is comparable to the miotic potency of carbachol or serotonin. All of these peptides share a C-terminal sequence Phe-X-Gly-Leu-Met-NH2 (where "X" is a variable amino acid) which is characteristic of all tachykinins. Six other biologically active peptides or the synthetic poly-DL-alanine had no measureable miotic effect on these preparations up to a final concentration of 1000 to 10,000 nM. The miotic effect of SP on the rat iris was effectively, but not completely antagonized by the presence of 10(-7)M atropine sulfate in the incubation medium. Preliminary results indicate that the miotic effect of physalaemin, eledoisin and eledoisin related peptide on the anterior segment of rat eyes is similarly antagonized by atropine.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D006224:Cricetinae; D004600:Eledoisin / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D008916:Miotics / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010803:Physalaemin / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013373:Substance P / Q000494:pharmacology
D008916:Miotics; D010446:Peptide Fragments; D010455:Peptides; C019092:substance P analog(eledoisin related peptide); D010803:Physalaemin; C019529:polyalanine; D013373:Substance P; C032682:substance P (4-11); D004600:Eledoisin; D001285:Atropine