Trends in Neurosciences
Volume 20, Issue 7, 1 July 1997, Pages 294-298
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Y-receptor subtypes—how many more?

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Abstract

The Y-receptors belong to the G protein-coupled receptor superfamily and mediate a wide variety of physiological effects, such as regulation of blood pressure, anxiety, memory retention, hormone release and food intake. Since the first human Y-receptor was cloned in 1992, the search for additional subtypes has been an area of intense study. Recently four new NPY-receptor subtypes have been isolated, revealing surprisingly limited sequence identity with values as low as 30%. Several reports indicate further heterogeneity of this receptor family, for example a peripheral Y2 receptor. However, since many studies have been carried out with different peptide analogs and radioligands in different species, there is substantial confusion regarding the pharmacological profile of the receptors. This may have led to an exaggeration of the potential number of discrete receptors.

Section snippets

Cloned receptor subtypes

The use of various cloning techniques has resulted in the identification of five receptors to date (Y1, Y2, Y4, Y5 and y6, see Table 1). Sequence analyses of the cloned receptors reveal a substantial divergence in primary sequence between the receptor subtypes (see Fig. 1). The human Y1 subtype shares closest amino acid identity with the Y4 subtype (42%) and the non-active, human form of the y6 subtype (51%) (Table 2). Interestingly, homology to the Y5 and Y2 subtypes decreases to values as low

The Y3 subtype

A receptor recognized by NPY, but not PYY, has been proposed. This receptor, Y3, was first localized to the adrenal medulla where it inhibited the release of catecholamines[46]. The Y3 receptor has also been observed in cardiac membranes47, 48and in the brainstem, for example nucleus tractus solitarii (NTS)[49]. Recently, a thorough characterization of the Y3 receptor in rat brainstem was carried out with various porcine NPY/PYY chimeras and other ligands[50]. Results indicated that positions

Variations in the pharmacological characterization of receptors

The choice of binding assay, for example binding of radioligand to membranes or whole cells, can result in different agonist and antagonist affinities. Furthermore, the type of radioligand and the species origin of the peptides used in an assay can have a major influence on the pharmacological profile of a particular Y-receptor. Species origin probably has minor effects for conserved peptides like NPY or PYY. However, major alterations may be observed for the less conserved PP. The use of

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