Characterization and localization of pituitary adenylate cyclase-activating polypeptide (PACAP) binding sites in the brain of the frog Rana ridibunda

The biochemical characteristics and the distribution of pituitary adenylate cyclase-activating polypeptide (PACAP) binding sites have been investigate d in the brain of the frog Rana ridibunda by using [I-125]PACAP27 as a radi oligand. Membrane-binding studies revealed the existence of high-affinity r eceptors for frog PACAP38 and PACAP27. In contrast, the [Des-His(1)]PACAP38 analogue had a much lower affinity and vasoactive intestinal polypeptide d id not produce any displacement of the binding. Autoradiographic labeling o f frozen brain sections revealed that the highest concentrations of PACAP r eceptors were located in the olfactory bulb, pallium, striatum, habenular n uclei, ventromedial thalamic nucleus, corpus geniculatum, posterior tubercl e, dorsal part of the magnocellular preoptic nucleus, tectum, and the molec ular cell layer of the cerebellum. Moderate binding was observed in the sep tum, in most parts of the thalamus, the dorsal hypothalamic nucleus, the me dian eminence, the ventral nuclei of the tegmentum, the torus semicirculari s, and the interpeduncular and isthmi nuclei. The present data provide the first biochemical characterization and anatomic distribution of PACAP bindi ng sites in the brain of a nonmammalian vertebrate species. The widespread distribution of specific PACAP receptors in the frog brain suggests that th e peptide does not act solely as a hypophysiotropic factor, but likely fulf ills neurotransmitter functions, neuromodulator functions, or both. J. Comp . Neurol. 412:218-228, 1999. (C) 1999 Wiley-Liss, Inc.