Characterization of ocular receptors for pituitary adenylate cyclase activating polypeptide (PACAP) and their coupling to adenylate cyclase.
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 uvea had mainly (approximately 80%) non-selective VIP/PACAP receptors, but a small amount of selective PACAP receptors was detected. In the retina, the selective PACAP receptor predominated (approximately 85%), while the choroid (including the retinal pigment epithelium) had approximately 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Nilsson
S F
SF
Department of Biochemistry and Nutrition, Université Libre de Bruxelles, Belgium.
De Neef
P
P
Robberecht
P
P
Christophe
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002829:Choroid / Q000378:metabolism; D002924:Ciliary Body / Q000378:metabolism; D046508:Culture Techniques; D000242:Cyclic AMP / Q000096:biosynthesis; D005123:Eye / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007498:Iris / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011817:Rabbits; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D007457:Iodine Radioisotopes; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases