Purpose: Pituitary adenylate cyclase-activating peptide (PACAP) is a sensory neuropeptide in the eye that is released by noxious stimuli and considered to be a mediator of the neurogenic ocular injury response, including miosis. The purpose of this study was to clarify the functional role of PACAP in iris sphincter and dilator muscles.
Methods: Iris sphincter and dilator muscles were isolated from rabbit eyes, and the effect of PACAP on mechanical responses of these muscles using isometric tension-recording methods was investigated.
Results: The iris sphincter responded to electric field stimulation with contractions composed of fast twitch and subsequent slow components. Both PACAP 27 and PACAP 38 enhanced the twitch response, but neither had an effect on the slow response. The effect of both PACAPs on the twitch response was dose dependent. Neither PACAP had an effect on the amplitude of contraction evoked by exogenously applied Ach. For the iris dilator muscle, PACAP 27 inhibited the contractions induced by field stimulation or phenylephrine, whereas PACAP 38 had no effect.
Conclusions: Both PACAP 27 and PACAP 38 enhance cholinergic transmission in sphincter muscle. The PACAP 27 induces relaxation of the dilator muscle by a direct effect on the muscle itself. The PACAP released during an ocular inflammatory response may induce miosis by the enhancement of cholinergic stimulation of the iris sphincter and by direct relaxation of the dilator muscles.