Résumé : Pituitary adenylate cyclase activating polypeptide (PACAP), a recently discovered neuropeptide, has large structural homology with vasoactive intestinal polypeptide (VIP). Two molecular forms exist, one with 27 (PACAP-27) and one with 38 (PACAP-38) amino acids. PACAP-27 is identical to the N-terminal of PACAP-38. Two major types of PACAP receptors have been identified; selective PACAP receptors, which bind PACAP with a much higher affinity than VIP, and non-selective VIP/PACAP receptors, which bind PACAP and VIP with equally high affinity. In the present investigation, PACAP receptors in different parts of the albino rabbit eye, and their coupling to adenylate cyclase were characterized. Crude tissue homogenates from iris, ciliary body, retina and choroid were used. Competition binding curves were established for VIP, PACAP-27 and PACAP-38, with [125I]VIP or [125I-Acetyl-His1]PACAP-27 as tracer. The effects on adenylate cyclase activity were determined by plotting dose-response curves (10-10-10-6 M) for VIP, PACAP-27 and PACAP-38. The anterior urea had mainly (∼ 80%) non-selective VIP/PACAP receptors, but a small amount of selective PACAP receptors was detected. In the retina, the selective PACAP receptor predominated (∼ 85%), while the choroid (including the retinal pigment epithelium) had ∼ 60% selective PACAP receptors. PACAP-27 and PACAP-38 stimulated the formation of cAMP with the same efficacy: 6·9-fold in the ciliary body, 3·6-fold in the iris, 5·1-fold in the retina and 2·3-fold in the choroid. VIP appeared to have only slightly less efficacy than PACAP in the anterior urea, and the difference in potency between the three peptides was small (EC50 values in the range 2-10 nM). In the retina and choroid, VIP had clearly less efficacy than PACAP, but the EC50 values for the VIP-stimulated adenylate cyclase activity were about the same as those for PACAP. The present investigation shows that both types of PACAP receptors are present in all intraocular tissues, but in different proportions. The predominance of selective PACAP receptors in the retina and choroid suggests that PACAP may have distinct effects, which are not shared by VIP. While in the anterior urea, PACAP and VIP are likely to have similar effects. The exact localization (e.g. blood vessels, epithelia, smooth muscles and neuronal cells) of the PACAP receptors within the different tissues remains to be determined. © 1994 Academic Press. All rights reserved.