G subtypes

Liu YF, Ghahremani MH, Rasenick MM, Jakobs KH, Albert PR. Stimulation of cAMP synthesis by Grcoupled receptors upon ablation of distinct G(XI protein expression. G, subtype specificity of the 5-HT1A receptor. J Biol Chem 1999 274 16,444-16,650. 

Hirasawa A, Sugawara T, Awaji T, Tsumaya K, Ito H, Tsujimoto G. Subtype-specific differences in subcellular localization of a,-adrenoceptors chlorethyl-clonidine preferentially alkylates the accessible cell surface a,-adrenoceptors irrespective of the subtype. Mol Pharmacol 1997 52 764-770. 

The initial subdivision of the a,-AR into subtypes was based primarily on the selectivity of WB-4101 for the aj -subtype [4] and the selective alkylation of the a,g-subtype shown by cbloroethylclonidine (CEC) [5]. Other antagonists selective for the a, -AR have been identified, such as 5-methyhirapidil [9] and (SH+Vniguld ine [10]. 

Richardson, B. P., Engel, G., Donatsch, P., and Stadler, P. A. (1985). Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs. Nature 316 126-131. 

Two AR subtypes, Ax and A3, couple through G to inhibit adenylate cyclase, while the other two subtypes, A2a and A2B, stimulate adenylate cyclase through Gs or G0if (for A2a). The A2BAR is also coupled to the activation of PLC through Gq. Furthermore, each of these receptors may couple through the (3,y subunits of the G proteins to other effector systems, including ion channels and phospholipases. Levels of intracellular... 

Opioids act on heptahelical G-protein-coupled receptors. Three types of opioid receptors (p, 8, k) have been cloned. Additional subtypes (e.g., pl3 p2, 81 82), possibly resulting from gene polymorphisms, splice variants or alternative processing have been proposed. Opioid receptors are localized and can be activated... 

The antimuscarinic drug atropine, and its derivative ipratropiumbromide, can also be used for antiarrhyth-mic treatment. Muscarinic receptors (M2 subtype) are mainly present in supraventricular tissue and in the AV node. They inhibit adenylylcyclase via G proteins and thereby reduce intracellular cAMP. On the other hand, activation of the M2 receptor leads to opening of hyperpolarizing Ik.acii and inhibits the pacemaker current If probably via the (3y-subunit of the Gi protein associated with this receptor. The results are hyperpolarization and slower spontaneous depolarization. Muscarinic receptor antagonists like atropine lead to increased heart rate and accelerated atrioventricular conduction. There are no or only slight effects on the ventricular electrophysiology. 

These findings demonstrate that subtype-selective diugs are likely to be of benefit, e.g., as anxiolytics... 

A number of agonists can act through several receptor classes, e.g., ion channels and G-protein-coupled receptors. To set receptor subtypes permanently linked to ion channels ( ligand-gated ion channels) apart... 

For differentiation of G-protein-coupled receptor sub-types from subtypes permanently linked to ion channels (ligand-gated ion channels) the terms metabotropic versus ionotropic receptors, respectively, are used. Prime examples of metabotropic receptors are given by the lnGlu receptor family of G-protein-coupled glutamate receptors. 

At a cellular level, the activation of mAChRs leads to a wide spectrum of biochemical and electrophysiological responses [1, 5]. The precise pattern of responses that can be observed does not only depend on the nature of the activated G proteins (receptor subtypes) but also on which specific components of different signaling cascades (e.g. effector enzymes or ion channels) are actually expressed in the studied cell type or tissue. The observed effects can be caused by direct interactions of the activated G protein(s) with effector enzymes or ion channels or may be mediated by second messengers (Ca2+, DP3, etc.) generated upon mAChR stimulation. 

As to be expected from a peptide that has been highly conserved during evolution, NPY has many effects, e.g. in the central and peripheral nervous system, in the cardiovascular, metabolic and reproductive system. Central effects include a potent stimulation of food intake and appetite control [2], anxiolytic effects, anti-seizure activity and various forms of neuroendocrine modulation. In the central and peripheral nervous system NPY receptors (mostly Y2 subtype) mediate prejunctional inhibition of neurotransmitter release. In the periphery NPY is a potent direct vasoconstrictor, and it potentiates vasoconstriction by other agents (mostly via Yi receptors) despite reductions of renal blood flow, NPY enhances diuresis and natriuresis. NPY can inhibit pancreatic insulin release and inhibit lipolysis in adipocytes. It also can regulate gut motility and gastrointestinal and renal epithelial secretion. 

While these functions can be a carried out by a single transporter isoform (e.g., the serotonin transporter, SERT) they may be split into separate processes carried out by distinct transporter subtypes, or in the case of acetylcholine, by a degrading enzyme. Termination of cholinergic neurotransmission is due to acetylcholinesterase which hydrolyses the ester bond to release choline and acetic acid. Reuptake of choline into the nerve cell is afforded by a high affinity transporter (CHT of the SLC5 gene family). 

---