Receptor-channel coupling, types

Fig. 1. Schematic drawing of the cholinergic neurotransmission. In case of ganglionic and neuro-muscular synapses, the receptor is of the nicotinic, sodium channel-coupled type, in case of synapses at the parasympathetic target organs, the receptor is of the muscarinic, G-protein-coupled type. The predominant ehinination pathway of the transmitter acetylcholine...

Sorcin (soluble resistance-related calcium binding protein) was isolated from multidrug-resistant cells and is expressed in a few mammalian tissues such as skeletal muscle, heart, and brain. In the heart, sorcin interacts with the ryanodine receptor and L-type Ca2+-channels regulating excitation in contraction coupling. 

Kammermeier, P J., Xiao, B., Tu, J. C., Worley, P F., and Ikeda, S. R. (2000) Homer proteins regulate coupling of group I metabotropic glutamate receptors to N-type calcium and M-type potassium channels../. Neurosci. 20,7238-7245. 

In mice carrying the mutated a2A-D79N receptor gene, presynaptic function in the vas deferens did not differ from wild-type control mice (Altman et al. 1999). This finding indicates (1) that channel coupling is not required for presynaptic function of a2A-receptors in sympathetic nerves and (2) that there is a high number of spare receptors at the presynaptic site, as expression of the a2A-D79N receptor was found to be reduced to 20% of the wUd-type level (MacMillan et al. 1996). Thus, Ca channels in presynaptic nerve terminals are essential for neurotransmitter release, and current... 

Bertrand S et al. The anticonvulsant, antihyperalgesic agent gabapentin is an agonist at brain gamma-aminobutyric acid type B receptors negatively coupled to voltage-dependent calcium channels. J Pharmacol Exper Therap 2001 298 15-24. 

The biological effects of histamine (Table 15.1) are mediated via three receptor subtypes, HI, H2 and H3 that are linked to G protein but activate different cell-signalling systems. The histamine HI receptor is associated with the phospholipase C-catalysed formation of inositol 1,4,5-triphosphate (IP3) and 1,2-diacylglycerol (DAG). The H2-receptor is coupled to adenylyl cyclase, increasing the production of cAMP. The cellular messenger system involved in H3-receptor activation has not been fully defined, but it may couple to N-type Ca2+-channels. The genes encoding for HI and H2 receptors have been cloned. A mutation of the human H2 receptor has been linked to schizophrenia. 

Opioid receptors. Direct binding of highly radioactive opiates has permitted localization of specific opiate receptors of several types.863-866 The three major types (p, 8, k) are all 7-helix receptors coupled to adenylate cyclase, K+ and Ca2+ channels, and the MAP kinase cascade.866 The p receptors bind morphine most tightly.867 8673 These receptors are found in various cortical and subcortical regions of the brain. Most narcotics are polycyclic in nature and share the grouping indicated in Fig. 30-30. However, the flexible molecule methadone binds to the same receptors.868 Among antagonists that block the euphoric effects of opiates the most effective is naloxone (Fig. 30-30). 

Jarolimek W, Misgeld U (1997) GABAB receptor-mediated inhibition of tetrodotoxin-resistant GABA release in rodent hippocampal CA1 pyramidal cells. J Neurosci 17 1025-32 Jeong SW, Ikeda SR (2000a) Effect of G protein heterotrimer composition on coupling of neurotransmitter receptors to N-type Ca(2+) channel modulation in sympathetic neurons. Proc Natl Acad Sci USA 97 907-12... 

Fig. 3 Mechanisms involved in presynaptic inhibition through P2Y receptors. P2Yi 2,4,12 receptors may couple to PTX-sensitive proteins and mediate voltage-dependent inhibition of calcium currents by direct interaction of the Py subunits with the N-type VSCC (1). The P2Yi, 2,4 receptor subtypes may also couple to PTX-insensitive Gq/n proteins and mediate voltage-independent inhibition of Ca2+ currents by (2) direct interaction of G protein Py subunits with the channel or (3) activation of phospholipase C (PLC), causing depletion of membrane phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2).

Wu X, et al. A critical protein kinase C phosphorylation site on the 5-HT(lA) receptor controlling coupling to N-type calcium channels. J Physiol 2002 538(Pt 1) 41—51. 

The 5-HT1A receptors are coupled to potassium and calcium channels. Intracellular current-clamp recordings in slices containing the DR established that the 5-HT-mediated inhibition involved an increase in potassium conductance, which exhibits inward rectification (18,58). This induced a membrane hyperpolarization leading to a decrease in action potential frequency. Similar responses to 5-HT1A receptor activation have been reported in other neuronal types, such as hippocampal pyramidal cells (16,59) or 5-HT neurons of the caudal raphe nuclei (60). 

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