G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [1]. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialized database for GPCRs: http://www.gpcr.org/7tm/.

The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [2, 3, 4].

In the periphery, the adrenergic system plays an important role in regulating the cardiovascular system [5]. Increased sympathetic discharge to the heart increases the rate and force of contraction mediated through beta-1 receptors. Circulating adrenaline also acts on cardiac tissue, and, in addition, acts both on alpha-1 adrenoceptors in arterial smooth muscle, stimulating vasoconstriction, and on beta-2 adrenoceptors in vascular beds of skeletal muscle, stimulating vasodilation. In the CNS, noradrenaline is thought to be involved in the regulation of mood, and various psychoactive drugs alter noradrenergic function. Numerous drugs exert their actions via adrenoceptors: e.g., beta-2 selective agonists such as salbutamol are used in the acute treatment of asthma, while alpha agonists prolong the action of local anaesthetics, and act as nasal decongestants [5].

Adrenoceptors can be divided into three main classes based on sequence similarity, receptor pharmacology and signalling mechanisms. Further subdivisions exist within each class. A large number of agonists and antagonists distinguish between the different classes of adrenoceptor; by contrast, relatively small differences in agonist and antagonist affinities are demonstrated, especially within the alpha-1 and alpha-2 adrenoceptor subtypes [5].

The pharmacological profile of the alpha-1A receptor closely resembles that of the alpha-1D receptor . It appears to be widely distributed in the rat, with high levels in peripheral tissues (e.g., vas deferens) and in the CNS (e.g., hippocampus, cerebral cortex and brainstem). The receptor is coupled to the phosphoinositide pathway through a pertussis-toxin-insensitive G-protein, probably of the Gq/G11 class. It is thought to stimulate direct entry of extracellular calcium [5].

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