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) on pupil diameter and blood-aqueous barrier have been investigated in rabbits. The rabbits, which were pretreated with indomethacin and a muscarinic antagonist (biperiden), responded with miosis to both CGRP fragments. CGRP(8-37) was much more potent than CGRP(32-37) but one order of magnitude less potent than substance P. Nerve blockade with tetrodotoxin did not affect the response, indicating a direct effect on the iris sphincter muscle. Pre-treatment with the unselective tachykinin receptor antagonist spantide or the NK1 receptor selective antagonist GR82334 caused a rightward shift of the dose-response curves for both fragments, while the CCK receptor antagonist loxiglumide had no inhibitory effect. Neither of the fragments induced any marked leakage of Evans 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 acting as neurokinin receptor agonists.