Foreword

Abstract

Molecular biological studies have revealed that native D1 receptors are comprised of two receptor subtypes, termed D1/D1A and D1B/D5, each of which when expressed in various cell lines stimulates the activity of adenylate cyclase. These receptors are, however, distinguishable on the basis of their primary structure, chromosomal localization, mRNA, and protein distribution as well as in their expressed pharmacological profiles. D1A, D1B, D1C, and D1D receptors exhibit molecular, pharmacological, and functional attributes that unambiguously allow for their distinct classification in the vertebrate phylum as true D1 receptor subtypes. While most receptor genes have been characterized only in mammals, D1-like receptor gene diversity has been examined in a small set of other vertebrate species, particularly Xenopus luevis and Gallus domesticus. Although Xenopus D1C and chicken D1D receptors significantly differ from either vertebrate or mammalian D1A and D1B receptors on the basis of their amino acid sequence and distinct pharmacological profiles, the functional and evolutionary relationship between these receptors is unclear and raises a number of intriguing questions. To address these issues, studies have undertaken to clone the entire complement of D1-like receptor genes from a number of early and late diverging vertebrate species. The assignment of each cloned receptor to defined D1 receptor subtype has been achieved by combining molecular phylogeny, pharmacological, and functional approaches. While mammalian homologues of D1C and D1D receptors have yet to be found and may indeed have been lost during the course of mammalian evolutionary divergence, the widespread appearance of multiple D1 receptor subtypes throughout the vertebrate phylum suggest some gain or loss of function in mammals associated with these particular receptor subtypes.