EXPRESSION OF PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP) RECEPTORS AND PACAP IN HUMAN FETAL RETINA

Specific receptors for pituitary adenylate cyclase-activating polypept ide (PACAP), a novel peptide with neuroregulatory and neurotrophic fun ctions, have recently been identified in the retinas of different mamm alian species, In the present study, expression of PACAP receptors and PACAP was investigated in the retinas of 12-18-week human embryos. Ra dioligand binding studies showed that the two forms of PACAP with 38 a nd 27 amino acids (PACAP 38 and PACAP 27, respectively) displaced the binding of I-125-PACAP 27 with IC50 values in the picomolar range, whe reas functional receptor assays demonstrated that the two peptides wer e potent and effective stimulators of adenylyl cyclase activity, In co ntrast, vasoactive intestinal peptide (VIP) and human peptide histidin e-isoleucine, which are homologous to PACAP, displayed lower affinitie s for the I-125-PACAP 27 binding site and were much less potent stimul ators of cyclic AMP formation. Glucagon and secretin were inactive in both receptor assays, The expression of specific PACAP receptors was f urther investigated by reverse transcription-polymerase chain reaction technique, which showed the presence of mRNAs coding for PACAP type I and for nonselective PACAP type II (both VIP1 and VIP2) receptors, By the same technique, expression of PACAP mRNA was also detected. These data indicate that the developing human retina synthesizes PACAP and that the peptide may act on retinal cells by predominantly stimulating PACAP type I receptors coupled to cyclic AMP formation.