Adrenergic receptor effector systems

Thus three lines of evidence define the rapidly dissociating receptor as the LR complex. Conditions known to uncouple R from G--first, guanine nucleotide and second, pertussis toxin—produce LR third, reconstitution of G protein restores receptor affinity, sensitivity to guanine nucleotide, and effector activation. In this sense, the ligand and binding behavior of this system is analogous to that of the beta-adrenergic receptor, where the LR and LRG complexes have already been studied with purified proteins and reconstituted membrane preparations (2,i0). 

Fig. 5.12 (a) Synaptic types along dendritic spines of M/T and GC units uni-, and bi-directional junctions, (b) Transmitter systems at a reciprocal synapse, Mitral-Granule cell junction. [Glu, glutamate (R, receptor) GABA, y-aminobutyric acid (R, receptor) E, intracellular effector and aAR, alpha-adrenergic receptor.]. (From Hayashi et al., 1993.)... 

Two isoforms of D2R are produced by alternative splicing, generating a long D2 receptor (D2L) and a shorter form (D2S) that differ by 29 amino acids in the third intracellular loop (Dal Toso et al., 1989). As the importance of the third intracellular loop for selective coupling to specific G-protein/effector systems has been shown by studies on other receptors (muscarinic and adrenergic receptors) (Kubo et al., 1988 Cotecchia et al., 1992), it is not surprising that differences in the G-protein coupling exists between the two isoforms of D2R. 

Very commonly, a target tissue will be stimulated by the S3mipathetic system and inhibited by the paras5mipathet-ic system, or vice versa. Examples are found in table 7.1. Among the paras mipathetic responses listed there, we find stimulation of smooth muscle in the bronchi, and relaxation of smooth muscle in the arterioles both are mediated by muscarinic acetylcholine receptors (cf. Figure 7.6). Here, we have an example of diverse effector mechanisms triggered from similar receptors. Similarly, the adrenergic receptors can operate different intracellular switches as needed. These different effector mechanisms are covered in some more detail in the chapter on G protein-coupled receptors. 

Lakhlani PP, Lovinger DM, Limbird LE. Genetic evidence for involvement of multiple effector systems in a2A-adrenergic receptor inhibition of stimulus-secretion coupling. Mol Pharmacol 1996 50 96-103. 

A variety of responses in the body to different adrenergic drugs are based on their relative selectivity when binding with various receptors, which are exclusively found in and unevenly distributed in effector structures (heart, cardiovascular system, lungs, brain, peripheral nervous system, etc.). 

Sympathetic arc involved in blood pressure regulation and sites where drugs may act to influence the system. A. Receptors on effector cell. 6. Adrenergic varicosity. C. Nicotinic receptors (postganglionic fibers). D. Brainstem nuclei. NTS, nucleus of the tractus solitarii VMC, vasomotor center ACh, acetylcholine NE, norepinephrine a, a-adrenoceptors (3, 13-adrenoceptors P2, P2-purinoceptors ATR adenosine triphosphate. 

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