Muscarinic acetylcholine receptors in invertebrates: comparisons with homologous receptors from vertebrates.

ABSTRACT

The pharmacology, physiology and molecular biology of invertebrate muscarinic acetylcholine receptors are compared with current knowledge concerning vertebrate muscarinic acetylcholine receptors. Evidence for the existence of multiple receptor subtypes in invertebrates is examined, emphasizing what is presently known about the sensitivity of invertebrate preparations to subtype selective ligands previously defined in vertebrate studies. Other evidence for muscarinic receptor subtypes which is examined includes heterogeneous responses to classical muscarinic ligands and evidence for coupling of invertebrate muscarinic receptors to several different classes of second messenger systems. Clues regarding possible functions for invertebrate muscarinic receptors are discussed, including evidence from both physiological studies and in situ localization studies which reveal patterns of receptor protein and mRNA expression. A detailed analysis of the structural similarities between a cloned Drosophila muscarinic receptor and vertebrate muscarinic receptors is also presented. Regions of the receptors that may be involved in ligand binding, effector coupling and receptor regulation are identified in this comparison. Future directions for invertebrate muscarinic receptor research are considered including methods for cloning other receptor subtypes, methods for cloning homologous receptors from other species and genetic approaches for determining the physiological roles of muscarinic receptors.