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Biologically active peptides modulate pupillary responsiveness in many non-primate mammals. We examined the action of seven different peptides on iris sphincter and dilator muscles of rhesus monkey. Iris sphincter and dilator muscle preparations from rhesus monkeys were mounted in an organ bath, and tension changes were recorded by an isometric transducer. Electrical field stimulation (100 Hz, 0·3 msec, 10 V) was applied through a pair of platinum plate electrodes. Monkey iris sphincter and dilator muscles produced simple cholinergic and adrenergic excitatory responses respectively to electrical field stimulation. Strong field stimulation did not elicit slow Substance P (SP) mediated contractions like those in rabbit iris sphincter. Exogenously applied pituitary adenylate cyclase-activating peptide (PACAP) enhanced in a concentration-dependent manner (0·3 nM–0·1 μm) the sphincter response to field stimulation, while neuropeptide Y (NPY) and somatostatin (SRIF) attenuated it. These three peptides did not affect sphincter contractions induced by acetylcholine, and therefore were acting at presynaptically. SP, calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and galanin (GAL) had no effect (at 0·1 μm) on iris sphincter. None of seven exogenously applied peptides had an effect on monkey iris dilator muscle. The innervation of primate irises may be relatively simple compared to non-primates because each of the peptides in this study can modulate miosis or mydriasis in non-primate mammals. Future studies will be expected on the functional significance of species differences in iridial innervation.