A Comparison of P₁‐ and P₂‐Purinoceptors

Abstract

INTRODUCTIONIn 1978, Burnstock' proposed a system for the classification of the receptors at which adenosine and adenine nucleotides act to produce their diverse and numerous effects. This proposal was based on a review of the extensive literature concerning the actions of purine nucleosides and nucleotides on a wide variety of tissues. This classification system termed the receptors at which the purine nucleosides and nucleotides act purinoceptors and proposed that there were two major subtypes, the PI-and P,purinoceptors. This classification system was based on four criteria:1. The relative potencies as agonists of adenosine, AMP, ADP, and ATP 2. The selective actions of antagonists, particularly methylxanthines such as theo-3. The activation of adenylate cyclase by adenosine but not by ATP. 4. The induction of prostaglandin synthesis by ATP but not by adenosine. ph ylline.According to this classification, P,-purinoceptors are more responsive to adenosine and AMP than to ADP and ATP. Methylxanthines such as caffeine and theophylline are selective antagonists at these P,-purinoceptors, and occupation of these receptors alters the activity of adenylate cyclase. P2-purinoceptors are more responsive to ADP and ATP than to adenosine and AMP. Methylxanthines are Classification systems for the receptors for adenosine were independently proposed by Van Calker eta[.' and Londos et al.' These classifications were based on the relative 165

Antidiuretic Effects of ATP Induced by Microinjection into the Hypothalamic Supraoptic Nucleus in Water-Loaded and Ethanol-Anesthetized Rats

“…On the other hand, the absence of any effect by ADP, AMP or adenosine injected into the SON on the urine outflow suggests that the effects of ATP are mediat ed mainly through an activation of P2-purinoceptors (11,18,19). These results also contrasts with those observed in the PVN, in which microinjection of ATP causes a more potent antidiuretic effect than that of adenosine and is not antagonized by theophylline (14).…”

Systemic and Myocardial Effects of ATP and Adenosine during Hypoxic Pulmonary Hypertension in Lambs

“…A, receptors are present on the vascular endothelial cells, stimulate adenylate cyclase, and mediate the vasodilator effects of adenosine (21). P2 receptors are also classified into P2,, P2,, P,,, and P2, receptors (21). The relative predominance of these receptors on the cell varies between different organs, with P2, receptors being more predominant on vascular endothelial cells.…”

“…Based on receptor affinity and ligand binding studies, PI receptors have been further classified into A, and A, subtypes; A, receptors inhibit adenylate cyclase and appear predominantly in the heart, where they mediate the negative chronotropic and inotropic effects of adenosine (21). A, receptors are present on the vascular endothelial cells, stimulate adenylate cyclase, and mediate the vasodilator effects of adenosine (21). P2 receptors are also classified into P2,, P2,, P,,, and P2, receptors (21).…”

Signaling by Extracellular Nucleotides

“…Despite such difficulties, ATP (P 2 purinergic) receptors and adenosine (P 1 purinergic; also known as A 1 -A 3 ) receptors have been distinguished from each other based on the relative potency of various nucleoside and nucleotide agonists and by the differential actions of a limited and somewhat nonselective collection of antagonists (Burnstock 1978, Paton & Taerum 1990. Using similar criteria, ATP receptors have themselves been placed into distinct pharmacological subclasses (Burnstock & Kennedy 1985), and electrophysiological studies have shown that ATP can activate both G protein-coupled receptors that signal through the elaboration of cytoplasmic second messengers (metabotropic receptors) (O'Connor et al 1991) and ligand-gated channels that mediate direct and rapid increases in membrane ion conductance (ionotropic receptors) (Bean 1992).…”