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Fluorescence Investigations of Receptor-Mediated Processes

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Abstract

There are a number of receptor-coupled signal transduction systems which regulate the levels of second messengers within the cell through the actions of at least three types of protein components. Specifically, these components are the receptor protein itself, a GTP-binding protein (G protein), and a biological effector which can be an enzyme or an ion channel (Gilman, 1987; Cerione et al., 1986; Neer and Clapham, 1988; Stryer et al., 1981). The G proteins function as transducers within these systems by mediating the regulation of effector activities by specific cell surface receptors. Among the types of biological activities which are regulated in this manner include hormonalregulated adenylate cyclase activity (Gilman, 1987; Cerione et al., 1986; Lefkowitz and Caron, 1988), vertebrate vision (Stryer et al., 1981; Fung, 1983), receptor-coupled phosphoinositide metabolism (Berridge and Irvine, 1984; Gomperts, 1983; Wallace and Fain, 1985; Bokoch and Gilman, 1984; Smith et al., 1986), arachidonic acid release (Burch et al., 1986; Jelsema and Axelrod, 1987), activation of Ca2+ channels found in excitatory cells (Hescheler et al., 1987; Yatani et al., 1987), and cardiac K+ channels (Codina et al., 1987; Logothetis et al., 1987). Various lines of evidence suggest that a common regulatory mechanism underlies the functioning of each of these signaling pathways. In all cases, the signal is initiated by the binding of an appropriate ligand (i.e., hormone) to the receptor, or in the case of visual transduction, by the absorption of light. This constitutes the activation of the receptor, thereby promoting the interaction of the receptor with the G protein. It is the formation of the receptor-G protein complex which is responsible for the exchange of a tightly bound molecule of GDP for GTP. The binding of GTP (or a nonhydrolyzable GTP analogue) then primes the G protein for interacting with the effector protein. This interaction is responsible for the regulation of the effector activity with the regulation persisting until the bound GTP is hydrolyzed to GDP. The GTPase activity results in the deactivation of the G protein and thereby provides the means by which the signaling system can return to its initial (resting) state.

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Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  1. 1.Department of PharmacologyCornell UniversityIthacaUSA

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