G-protein-coupled seven-transmembrane

Feng Y, Broder CC, Kennedy PE, Berger EA (1996) HIV-1 entry cofactor functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272 872-877 Fernandez EJ, LoUs E (2002) Structure, function, and inhibition of chemokines. Annu Rev Pharmacol Toxicol 42 469-499... 

It is universally accepted that the action of opioids is mediated by specific receptors. It is presumed that several types of opioid receptors exist p, k, 5, and a. A few of these are in turn subdivided into subtypes. It has been found that opioid receptors are seven transmembrane G-protein-coupled receptors that are localized in the membranous part of the synaptosomal head it has also been found that they are glycoproteins. They are prone to conformational changes in certain situations, which is essential for their selective binding with agonists or antagonists. 

Adrenergic transmission is well known to be involved in the regulation of homeostatic control through its functions in the autonomic nervous system. Additionally, adrenergic projections in the brain have been identified with important roles in neurocognition. Adrenoreceptors are seven transmembrane G-protein-coupled receptors that mediate the physiological responses of epinephrine and norepinephrine. The first classification of these receptors resolved a (alpha)-adrenoreceptors (aARs) from P (beta)-adrenoreceptors (PARs) (Ahlquist, 1948). Since then, additional subtypes and variants have been described. 

Opioid receptors are seven transmembrane G-protein coupled inhibitory receptors (Bockaert, 1991), although an association to excitatory G-proteins has also been reported (Varga et al., 2003). Intracellular signaling by these receptors involves the inhibition of adenylate cyclase with a subsequent decrease in cAMP levels (Surprenant et al., 1990), regulation of intracellular calcium levels, modulation of potassium channels (Williams et al., 2001), and control of MAP-kinase and ERK activity (Eitan et al., 2003 Varga et al., 2003). 

Subtypes of adenosine receptors exist - A, Aj and A3 -which have differential sensitivities to adenosine nucleoside analogues, including 2-methylthio-AMP, 2-thioadenosine, DPMA. IB-MECA, NECA, CPA. CCPA and DPCPX. These receptors, and subtypes within A2, have all been cloned. They have structures typical of the seven-transmembrane G-protein-coupled superfamily of receptors, but have amongst the shortest sequences known (A3 has only 318 amino acids), and a lack of sequence similarity with any other receptors appears to put them in a class of their own. Adenosine receptors are not sensitive to nucleotides such as ADP (adenosine diphosphate) and ATP (adenosine triphosphate), which instead act as P2 receptor agonists that are nucleotide-... 

Genes for both Bj- and B2-receptors, from several species including humans, have been cloned, sequenced and expressed. Both subtypes are of the seven-transmembrane G-protein-coupled superfamily. They can couple via the InsP3/DAG (Gq/ i) pathway, but commonly also activate phospholipase A2 which leads to liberation of prostaglandins. Also, activation of release of nitric oxide (NO) is common, and accounts for the prominent vasodilator action of bradykinin. Species-dependent subtypes have been demonstrated. and there is the possibility of alternative splicing. A proposed B3-receptor, originally described in the guinea-pig airways, appears to be a species-variant of the B2-receptor. 

The endothelins receptors are of the seven-transmembrane G-protein-coupled type, and couple mainly through the InsPs/DAG systems, though other mechanisms (including activation of tyrosine kinases and mitogenesis) may be involved. There are at least two receptor types encoded by different genes on different chromosomes. Also, there are species-dependent isoforms. The characteristics of the two receptors are as follows. 

GABAj receptors are of the seven-transmembrane G-protein-coupled type, and they have a widespread distribution in the body. Agonists at this receptor site include L-baclofen, CGP 27492 and CGP 35024. The receptors are negatively coupled to cAMP, and typical responses in neurons are to inhibit excitability by opening potassium channels or closing calcium channels. These inhibitory actions can be harnessed clinically for instance, baclofen is used as a muscle relaxant and has actions mainly at the spinal level within the GNS (see SKELETAL MUSCLE RELAXANTS). See GABA RECEPTOR ANTAGONISTS. 

Histamine H2-receptors are of the seven-transmembrane G-protein-coupled superfamily, and couple positively to the adenylyl cyclase (GJ pathway. Selective agonists include amthamine, dimaprit and impromidine. They also have actions at the other histamine receptor types impromidine and dimaprit have Hs-antagonist properties, and amthamine is a weak agonist at the H3 receptor. Also, 4(5)-methylhistamine has been used experimentally. 

These receptors are all of the seven-transmembrane G-protein-coupled types, and can couple negatively to adenylyl cyclase. 

---