TISSUE-SPECIFIC AND DEVELOPMENTAL EXPRESSION OF PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP) RECEPTORS IN RAT-BRAIN

The two forms of pituitary adenylate cyclase-activating polypeptide, P ACAP27 and PACAP38, are novel members of the vasoactive intestinal pep tide (VIP)/secretin/glucagon family of peptides. PACAP receptors that are positively coupled to adenylate cyclase and phospholipase C have b een recently identified. We examined the expression of PACAP receptors in the rat cortex, hippocampus, cerebellum and hypothalamus during po stnatal development. Functional studies revealed PACAP stimulation of cAMP formation in all the brain areas examined and [H-3]inositol monop hosphate ([H-3]InsP) accumulation only in the cerebellum and hypothala mus. Throughout development, the efficacy of PACAP in stimulating cAMP formation slightly increased in the cortex and hypothalamus and decre ased in the hippocampus and cerebellum; PACAP stimulation of [H-3]InsP formation decreased in the cerebellum and remained steady in the hypo thalamus. The effects of PACAP27 and PACAP38 on cAMP levels and inosit ol phospholipid hydrolysis were dose-dependent between 1 and 100 nM. I n the same brain areas, treatment with VIP increased cAMP formation at doses greater than 100 nM and failed to affect [H-3]InsP content, thu s suggesting the existence of type-I PACAP receptors. The reverse tran scription polymerase chain reaction (RT-PCR) was used to analyse the m RNA expression of type-I PACAP receptor splice variants. PACAP recepto r gene expression in the central nervous system was regulated in a dev elopmental- and tissue-specific manner. The PACAP-R transcript was det ected in all the brain areas examined whereas PACAP-R-hop mRNA occurre d only in the cerebellum and hypothalamus. The different expression pr ofiles and functional properties of PACAP receptors in the developing rat brain suggest an involvement of PACAP in histogenesis, maturation and neurotransmission.