Multimeric CREB-binding sites in the promoter regions of a family of G-protein-coupled receptors related to the vertebrate galanin and nociceptin/orphanin-FQ receptor families

Four related genes encoding a family of G-protein-coupled receptors (GPCRs) have been isolated from the mollusc Lymnaea stagnalis. The coding regions of this family of receptors share 97-99% sequence similarity at both the pr otein and nucleotide level, and they also share high sequence identity with vertebrate galanin and orphanin-FQ/nociceptin GPCR families. Analysis of t he promoter regions reveals shared domains, some of which encode highly con served repeating units. One 27-bp repeating unit, which encodes a c-AMP res ponse element (CRE) and binds CREB protein, is repeated 14 times in one pro moter. In situ hybridization showed expression of these receptors in identi fied neurons of several behaviourly important networks including those invo lved in feeding and ion and water regulation. These Lymnaea receptors are l ikely to represent members of a novel family of invertebrate neuropeptide r eceptors extensively regulated in response to intracellular signalling casc ades.