Classification Of Receptor Groups

Receptors are macromolecules that may or may not be a single molecular entity with multiple sites of interactions [4]. The hormone and neurotransmitter receptors present in the plasma membranes are transmembrane glycoproteins. The cy-tosolic receptors are soluble DNA-binding proteins that belong to a superfamily of nuclear receptors. The primary pharmacological classification of receptors for hormones or neurotransmitters is based on the interaction with synthetic ligands or drugs. Norepinephrine acts on two types of receptors, they are named a- and P-adrenoceptors on the basis of the rank order of potencies for norepinephrine, epinephrine, and other analogs [4,5]. With the discovery of selective a- and P-adrenoceptor antagonists, a-adrenoceptors were differentiated as a1 and a2-adre-noceptors, and based on the agonist interactions P-adrenoceptors were further characterized as P1-, P2-, and P3-adrenoceptors. The structural diversity and multiplicity of a hormone or neurotransmitter receptor subtypes cannot be predicted only on pharmacological data. The current classification criteria recommended by the Committee for Receptor Nomenclature and Drug Classification of the International Union of Pharmacology (IUPHAR) is based on a combination of molecular structure (structural), signal transduction mechanism (transduction), and receptor function (premonitory or operational) [2,6]. The structures and functions of a number of receptors have now been elucidated. Advances in molecular biology also make it possible to determine amino acid sequence of receptors.

Based on structural and transductional characteristics, receptors can be classified into four groups [2,3]: (1) receptors with a single transmembrane segment,

(2) oligomeric receptors with both ligand-binding sites and ion channel complexes, (3) G-protein coupled receptors linked to G-proteins, and (4) nuclear receptors, which are cytosolic, soluble DNA-binding proteins. Receptors can also be classified into superfamilies based on sequence (structure) similarities, which include many receptor proteins that differ pharmacologically but are functionally similar [2], e.g., G-protein coupled receptors (GPCRs), ligand gated-ion channel receptors (LGCRs), voltage-gated-ion channel receptors (VGCRs), tyrosine ki-nase receptors, tyrosine phosphatase receptors, hematopoietic cytokine receptors, and nuclear receptors. Receptors in each superfamily may be further subclassified into receptor families, and usually they have been named with reference to their endogenous ligands, e.g., neuropeptide Y, endothelin, and epidermal growth factor. Each family of receptors can be classified into subtypes on the basis of relative sequence homologies and functional and signal transduction mechanisms, e.g., neuropeptide Y receptor Y1 (NPYR-Y1), NPYR-Y2, NPYR-Y-Y3, NPYR4, and NPYR-Y5, which show characteristic rank order of potency for antagonist or agonist affinities for each subtype. Different receptor families in a superfamily will have similar structure though there may not be good sequence homology (~ 20%). Within a receptor family, members of a subfamily are structurally more closely related (~ 50-80%), and each subtype single polypeptide is encoded by distinct gene. In the case of multisubunit oligomeric receptors (LGCR superfam-ily), each subtype receptor may be made of subunits of different isoforms (iso-forms in each family are highly homologous, > 70% identity). The receptors are basically either membrane or cytoplasmic receptors.

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