Keywords

Purinergic signalling was proposed in 1972 (Burnstock 1972) and purinergic receptors defined in 1976 (Burnstock 1976). In 1978, it was recognised that there were two families of purinoceptors, named P1 (adenosine) and P2 (nucleotide) receptors (Burnstock 1978). An edited book about purinergic receptors was published in 1981 (Burnstock 1981). Based on pharmacology, P2 receptors were later divided into P2X and P2Y subtypes (Burnstock and Kennedy 1985). P2Z (later named P2X7) receptors (Gordon 1986), P2T (later named P2Y12) receptors (Gordon 1986) and P2U (later named P2Y2 and/or P2Y4) receptors (O’Connor et al. 1991) followed. Important advances were made in the early nineties, when transduction mechanisms were identified (Dubyak and El Moatassim 1993) and P1, P2Y and P2X receptors cloned and characterised. Four subtypes of P1 receptors, A1, A2A, A2B and A3 receptors (Maenhaut et al. 1990; Fredholm et al. 1994), initially P2Y1 (Webb et al. 1993) and P2Y2 (Lustig et al. 1993) receptors and a year later P2X1 (Valera et al. 1994) and P2X2 (Brake et al. 1994) receptors were identified. These findings were rationalised by Abbracchio and Burnstock (Abbracchio and Burnstock 1994) by defining seven P2X ion channel receptor subtypes and eight P2Y G protein-coupled receptors. A popular comprehensive review about purinoceptors was published by Ralevic and Burnstock (1998) (4094 citations). An important study showed that three P2X receptor subtypes were combined to form trimer ion channels (Nicke et al. 1998) either as homomultimers and heteromultimers (Burnstock 2007a). Reviews about the expression and functions of purinergic receptors for many different cell types (Burnstock and Knight 2004) and the molecular pharmacology of P2X receptors (North 2002) are available and the elegant identification of the crystal structure of the P2X4 receptors (Fig. 1) (Kawate et al. 2009; Hattori and Gouaux 2012). Reviews about P1 (Fredholm et al. 2011; Chen et al. 2014), P2Y (Abbracchio et al. 2006; Erlinge 2011; Jacobson et al. 2015) and P2X (Müller 2015; Habermacher et al. 2016) receptors are available. A valuable book edited by Jacobson and Linden, entitled ‘Pharmacology of Purine and Pyrimidine Receptors’, was published in 2011 (Jacobson and Linden 2011).

Fig. 1
figure 1

The architecture of P2X receptors. Stereoview of the homotrimeric ΔzfP2X4 structure viewed parallel to the membrane. Each subunit is depicted in a different colour. N-acetylglucosamine (NAG) and glycosylated asparagine residues are shown in stick representation. The grey bars suggest the boundaries of the outer (out) and inner (in) leaflets of the membrane bilayer (Reproduced from Kawate et al. 2009, with permission from Nature Publishing Group)

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Purinoceptors modulate both short-term signalling in neurotransmission, neuromodulation and secretion and long-term (trophic) signalling in cell proliferation, differentiation and death in development and regeneration (see Burnstock 2016). Selective agonists and antagonists to purinoceptor subtypes currently available are summarised in Table 1. The evolution of purinoceptors (Burnstock 1996; Fountain and Burnstock 2009; Burnstock and Verkhratsky 2012) and the plasticity of expression and roles of purinoceptors in pathological conditions (Burnstock 2006, 2007b, 2013) have been reviewed. The intracellular expression of purinoceptors is being explored (Burnstock 2015) and the expression of purinoceptors during development and ageing has also been reviewed (Burnstock and Dale 2015). Detailed analysis of various aspects of purinoceptors will be presented in the following articles.

Table 1 Characteristics of purine-regulated receptors
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