Future Directions

Abstract

The purification of muscarinic receptor species from different tissues (Peterson et al., 1984; Haga and Haga, 1985; Berrie et ai., 1985; Wheatley et al., 1987; Baumgold et al., 1987) and the cloning of different muscarinic receptor proteins from pigs (Kubo et al., 1986a,b; Peralta et al., 1987b), humans (Bonner et al., 1987; Peralta et al., 1987a, 1988), and rats (Bonner et al., 1987) have opened the way for the investigation and clarification of a range of problems that could not previously be tackled. Within a short time, we will know the number of different muscarinic receptor proteins that are present in the genome of several species. To date, four muscarinic receptor proteins have been cloned and expressed (Kubo et al., 1986a,b; Fukuda et al., 1987; Bonner et al., 1987; Peralta et al., 1987a, 1988). From genomic blots of rat and human DNA, there may be 2–5 additional members of the muscarinic receptor gene family. These will need to be cloned, sequenced, and possibly expressed in order to determine whether some are pseudogenes. Between species, there is a very high homology between any given molecular subtype. For example, one rat amino acid sequence has a 98% identity to that cloned by Kubo et al. (1986a) from porcine brain. Between molecular subtypes, there is only 35–45% identity. Therefore, it is to be expected that a given molecular subtype will exhibit very similar binding and functional properties, irrespective of the mammalian species from which it is obtained. The homology between say, insect, avian, Torpedo, and mammalian muscarinic receptor sequences remains to be determined, although the binding properties of the receptors seem to be rather similar.