CGRP(8-37) AND CGRP(32-37) CONTRACT THE IRIS SPHINCTER IN THE RABBIT EYE - ANTAGONISM BY SPANTIDE AND GR82334

The effects of intracameral injections of CGRP(8-37) and CGRP(32-37) o n pupil diameter and blood-aqueous barrier have been investigated in r abbits. The rabbits, which were pretreated with indomethacin and a mus carinic antagonist (biperiden), responded with miosis to both CGRP fra gments. CGRP(8-37) was much more potent than CGRP(32-37) but one order of magnitude less potent than substance P. Nerve blockade with tetrod otoxin did not affect the response, indicating a direct effect on the iris sphincter muscle. Pre-treatment with the unselective tachykinin r eceptor antagonist spantide or the NK, receptor selective antagonist G R82334 caused a rightward shift of the dose-response curves for both f ragments, while the CCK receptor antagonist loxiglumide had no inhibit ory effect. Neither of the fragments induced any marked leakage of Eva ns blue into the aqueous humor indicating that there was no agonistic interaction with CGRP receptors in the eye. We conclude that CGRP(8-37 ) and CGRP(32-37) are miotic agents in the rabbit eye, possibly by act ing as neurokinin receptor agonists.