Evaluation of a co-facilitated information and learning programme for service users: the EOLAS programme.

BACKGROUND: The co-production and co-facilitation of recovery-focused education programmes is one way in which service users may be meaningfully involved as partners. OBJECTIVES: To evaluate the impact of a clinician and peer co-facilitated information programme on service users' knowledge, confidence, recovery attitudes, advocacy and hope, and to explore their experience of the programme. METHODS: A sequential design was used involving a pre-post survey to assess changes in knowledge, confidence, advocacy, recovery attitudes and hope following programme participation. In addition, semi-structured interviews with programme participants were completed. Fifty-three participants completed both pre- and post-surveys and twelve individuals consented to interviews. RESULTS: The results demonstrated statistically significant changes in service users' knowledge about mental health issues, confidence and advocacy. These improvements were reflected in the themes which emerged from the interviews with participants (n = 12), who reported enhanced knowledge and awareness of distress and wellness, and a greater sense of hope. In addition, the peer influence helped to normalise experiences for participants, while the dual facilitation engendered equality of participation and increased the opportunity for meaningful collaboration between service users and practitioners. CONCLUSIONS: The evaluation highlights the potential strengths of a service user and clinician co-facilitated education programme that acknowledges and respects the difference between the knowledge gained through self-experience and the knowledge gained through formal learning.

Evaluation of the binding to fixed platelets of agonists and antagonists of ADP-induced aggregation.

Steady state binding of eleven different ADP analogues to formaldehyde-fixed platelets has been determined in a competitive binding assay using 3H-ADP. The compounds tested were the inactive analogues L-ADP and L-ATP; the agonists 2-chloroadenosine 5'-diphosphate, adenosine 5'-O-(2-thiodiphosphate) and the diasteroisomeric pair Sp-adenosine 5'-(1-thiodiphosphate) (Sp-ADP-alpha-S) and Rp-adenosine 5'-(1-thiodiphosphate) (Rp-ADP-alpha-S); and the antagonists adenosine 5'-O-thiomonophosphate, 2-chloroadenosine 5'-O-thiomonophosphate, 2-choloroadenosine 5'-triphosphate, and the diastereoisomeric pair 5'-(1-thiotriphosphate) (Sp-ATP-alpha-S) and RP-adenosine 5'-(1-thiotriphosphate) (Rp-ATP-alpha-S). All compounds tested competed at the high affinity binding sites for ADP previously identified (Blood 1988; 71: 110-6) but in some cases competition could not be demonstrated at the low affinity sites because of the high nucleotide concentrations required. As a group, C2-substituted analogues bound less strongly (Ki greater than 2 micro M) than did the analogues without substituents in the purine ring (Ki less than 0.7 microM). With the pair of diastereoisomeric agonists Sp-ADP-alpha-S and Rp-ADP-alpha-S the Ki values at the high affinity site (210 nM and 560 nM) were of the same relative magnitude and in the same direction as their reported potencies as agonists (Ki 4 microM and 20 microM). With the diastereoisomeric antagonists Sp-ATP-alpha-S and Rp-ATP-alpha-S a similar relationship was seen between affinity (17 nM and 156 nM) and inhibitory potency (Ki 4 microM and 20 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Specific but noncompetitive inhibition by 2-alkylthio analogues of adenosine 5'-monophosphate and adenosine 5'-triphosphate of human platelet aggregation induced by adenosine 5'-diphosphate.

Some 2-alkylthio derivatives of adenosine 5'-monophosphate (AMP), adenosine 5'-monophosphorothioate (AMPS) and adenosine 5'-triphosphate (ATP) were examined as inhibitors of human platelet aggregation. 2-Methylthio-AMP, 2-ethylthio-AMP, 2-(pentan-l-yl)thio-AMP, 2-ethylthio-AMPS, 2-methylthio-ATP and 2-ethylthio-ATP (100 microM) each inhibited aggregation induced by adenosine 5'-diphosphate (ADP) but not by 11 alpha, 9 alpha-epoxymethano prostaglandin H2, a stable endoperoxide analogue. Log dose-response curves to ADP in the absence and presence of each inhibitor were not parallel and the inhibition could not be overcome by high concentrations of ADP. The ATP analogues achieved greater inhibition of aggregation induced by ADP (5 microM) than did the AMP analogues. The order of potency of the AMP analogues was 2-ethylthio-AMPS greater than 2-ethylthio-AMP greater than 2-(pentan-l-yl)thio-AMP greater than 2-methylthio-AMP, and 2-methylthio-ATP was more potent than 2-ethylthio-ATP. These 2-alkylthio substituted analogues of AMP and ATP are specific but noncompetitive inhibitors of ADP-induced human platelet aggregation.

Competitive inhibition by adenosine 5'-triphosphate of the actions on human platelets of 2-chloroadenosine 5'-diphosphate, 2-azidoadenosine 5'-diphosphate and 2-methylthioadenosine 5'-diphosphate.

1 Adenosine 5'-diphosphate (ADP) induces human platelet aggregation and noncompetitively inhibits stimulated human platelet adenylate cyclase; these two effects are mediated by the same ADP receptor, at which adenosine 5'-triphosphate (ATP) is a competitive antagonist. 2 Two ADP analogues, 2-azidoadenosine 5'-diphosphate (2-azido-ADP) and 2-methylthioadenosine 5'-diphosphate (2-methylthio-ADP) have been reported to be more potent as inhibitors of adenylate cyclase than they are as aggregating agents, but no evidence has been presented that these actions are mediated solely by the ADP receptor. 3 We therefore tested the ability of ATP to inhibit the actions of these compounds and of another ADP analogue, 2-chloroadenosine 5'-diphosphate (2-chloro-ADP). 4 2-Chloro-ADP, 2-azido-ADP and 2-methylthio-ADP each induced aggregation and inhibited stimulated adenylate cyclase. Both of these actions were competitively inhibited by ATP (50 microM) with pA2 values similar to those previously found for inhibition by ATP of these effects of ADP. 5 The reported greater potency of 2-azido-ADP and of 2-methylthio-ADP as inhibitors of adenylate cyclase than as aggregating agents is therefore due only to their greater efficacy for this effect, not to some extra actions elsewhere.

Some pharmacological and biochemical interactions of the enantiomers of adenylyl 5'-(beta, gamma-methylene)-diphosphonate with the guinea-pig urinary bladder.

Adenosine 5'-triphosphate (ATP) and adenylyl 5'-(beta, gamma-methylene)-diphosphonate (AMP-PCP) both contracted the guinea-pig urinary bladder, but the response to AMP-PCP was much greater. We synthesized the enantiomer of AMP-PCP, L-adenylyl 5'-(beta, gamma-methylene)-diphosphonate (L-AMP-PCP), and tested it on the guinea-pig bladder. L-AMP-PCP contracted the guinea-pig bladder, and was more potent than AMP-PCP and much more potent than ATP. The potential breakdown product of L-AMP-PCP, L-adenosine, unlike adenosine (the breakdown product of AMP-PCP), did not inhibit contractions of the guinea-pig bladder. ATP and its enantiomer L-adenosine 5'-triphosphate (L-ATP) were rapidly degraded by the muscle, and AMP-PCP was also degraded, but more slowly. L-AMP-PCP, however, was completely resistant to degradation. L-AMP-PCP would appear to be a useful ATP analogue, as it is potent and resistant to degradation, and its potential breakdown product, L-adenosine, is inactive.

Differential inhibition by adenosine or by prostaglandin E1 of human platelet aggregation induced by adenosine 5'-O-(1-thiodiphosphate) and adenosine 5'-O-(2-thiodiphosphate).

Adenosine 5'-diphosphate (ADP) induces human platelet aggregation and inhibits stimulated adenylate cyclase. Adenosine 5'-O-(1-thiodiphosphate) (ADP-alpha-S) and adenosine 5'-O-(2-thiodiphosphate) (ADP-beta-S) act at the ADP receptor and achieve the same maximal rate of human platelet aggregation as each other. Adenosine and prostaglandin E1, which noncompetitively inhibit ADP-induced aggregation by stimulating adenylate cyclase, inhibit aggregation induced by ADP-x-S more than aggregation induced by ADP-beta-S. ADP-x-S, unlike ADP-beta-S and ADP itself, does not inhibit stimulated adenylate cyclase. This suggests that the inhibition of stimulated adenylate cyclase by ADP, although not a cause of aggregation, may be of physiological importance in reducing the effects of endogenous agents such as adenosine and prostaglandins (for example, prostacyclin) to which the platelet may be exposed.

Adenosine 5-diphosphate antagonists and human platelets: no evidence that aggregation and inhibition of stimulated adenylate cyclase are mediated by different receptors.

1 Adenosine 5'-diphosphate (ADP) induces human platelet aggregation and noncompetitively inhibits stimulated human platelet adenylate cyclase; it has been suggested that these two effects are mediated by separate ADP receptors on the platelet surface. 2 Adenosine 5'-triphosphate and seven adenine nucleotide analogues were tested as inhibitors of both effects of ADP on human platelets, and were found to be competitive. 3 pA2 values were calculated for each antagonist for inhibition of both effects of ADP, and a good correlation (correlation coefficient 0.87; p less than 0.01) was found between the pA2 values for inhibition of ADP-induced aggregation and the pA2 values for inhibition of the effect of ADP on stimulated adenylate cyclase. 4 Such a correlation does not support the suggestion that ADP-induced aggregation and the inhibition by ADP of stimulated adenylate cyclase are mediated by two separate receptors.

5'-N-ethylcarboxamidoadenosine: a potent inhibitor of human platelet aggregation.

1 5'-N-ethylcarboxamidoadenosine (NECA) is an adenosine analogue which is 22,900 times more potent than adenosine as a vasodilator. Adenosine and some of its analogues are also inhibitors of human platelet aggregation. NECA was tested for its effects on human platelets. 2 NECA (1 microM) inhibited human platelet aggregation induced by adenosine 5'-diphosphate (ADP), adrenaline, 5-hydroxytryptamine (5-HT) and thrombin more powerfully than adenosine. NECA was 5 to 10 times more potent than adenosine at inhibiting ADP- and adrenaline-induced aggregation. 3 NECA, like adenosine, caused dose-dependent increases in levels of platelet adenosine 3',5'-cyclic monophosphate (cyclic AMP), which were competitively inhibited by theophylline, an adenosine antagonist. 4 These effects of NECA, like those of adenosine, were completely stereospecific as the L-enantiomer of NECA was inactive. 5 NECA did not interfere with the inhibition by ADP of prostaglandin E1 (PGE1)-stimulated adenylate cyclase. 6 NECA is the most potent analogue of adenosine tested so far on human platelets, and is the first example of a 5' modification to retain affinity for the platelet adenosine receptor.

Partial agonist behaviour of adenosine 5'-O-(2-thiodiphosphate) on human platelets.

1 The effects of an adenosine diphosphate (ADP) analogue, adenosine 5'-O-(2-thiodiphosphate) (ADP-beta-S), in which a terminal phosphate oxygen has been replaced by sulphur, were studied on human platelets. 2 ADP-beta-S induced platelet aggregation and inhibited prostaglandin E1 (PGE1)-stimulated adenylate cyclase but in both cases was less potent than ADP and did not achieve the same maximal effects. 3 Both actions of ADP could be inhibited by the simultaneous addition of ADP-beta-S (50 microM). 4 Aggregation induced by 11 alpha, 9 alpha-epoxymethano prostaglandin H2 (a stable endoperoxide analogue) was not inhibited by simultaneous addition of ADP-beta-S (50 microM). 5 The behaviour of ADP-beta-S towards human platelets was consistent with it being a partial agonist.

Effects of RP and SP diastereoisomers of adenosine 5'-O-(1-thiodiphosphate) on human platelets.

1 RP and SP diastereoisomers of adenosine 5'-O-(1-thiodiphosphate) ((R)-ADP-alpha-S and (S)-ADP-alpha-S), an adenosine 5'-diphosphate (ADP) analogue, were tested on intact human platelets. 2 Each diastereoisomer induced aggregation, (S)-ADP-alpha-S being 5 times more potent than (R)-ADP-alpha-S but they achieved only 75% of the maximal effect of ADP. 3 Aggregation induced by each diastereoisomer was competitively inhibited by ATP (50 microM). 4 Simultaneous addition of each diastereoisomer inhibited aggregation induced by ADP but not by 11 alpha, 9 alpha-epoxymethano prostaglandin H2, a stable endoperoxide analogue. Both diastereoisomers are therefore partial agonists at the ADP receptor mediating aggregation. 5 Unlike ADP, neither diastereoisomer inhibited prostaglandin E1 (PGE1)-stimulated adenylate cyclase, but each competitively inhibited the effect of aDP, with (S)-ADP-alpha-S again being 5 times more potent than (R)-ADP-alpha-S. 6 These are the first reported examples of ADP analogues to induce platelet aggregation without inhibiting PGE1-stimulated adenylate cyclase.

Absence of P2-purinoceptors in hippocampal pathways.

1. Many apparent actions of adenosine 5'-triphosphate (ATP) are mediated by adenosine produced by enzymatic hydrolysis of the nucleotide. Previously described actions of ATP in the CNS have been partly due to this phenomenon. In the present study analogues of ATP, which are not hydrolysed to adenosine, were used to seek responses to activating nucleotide (P2) receptors in the hippocampus. The analogues used were L-adenosine-5'-(beta,gamma-methylene)-triphosphonate and 2-methylthioadenosine-5'-(beta,gamma-difluoromethylene)-triphosphonat e. 2. Neither of the stable nucleotides had any effect on orthodromically evoked synaptic potentials in the CA1 region of rat hippocampal slices. Adenosine and ATP had inhibitory actions that could be prevented by the P1-receptor blocker 8-phenyltheophylline. 3. The stable nucleotides had no consistent effects on the firing rate of single neurones in stratum pyramidale of the CA1 region, although adenosine and ATP produced a xanthine-sensitive inhibition. 4. Adenosine selectively reduced the sensitivity of CA1 neurones to microiontophoretically applied carbachol whereas stable nucleotides did not. 5. It is concluded that there are neither P2x- nor P2y-receptors for adenine nucleotides on rat hippocampal CA1 pyramidal cells at the Schaffer collateral and commissural terminals in stratum radiatum.

Relaxation of isolated taenia coli of guinea-pig by enantiomers of 2-azido analogues of adenosine and adenine nucleotides.

1 2-Azido photoaffinity analogues of adenosine 5'triphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP), and adenosine have been synthesized and tested on guinea-pig taenia coli. 2 2-Azido-ATP and 2-azido-ADP were approximately 20 times more potent than ATP as relaxants of taenia coli, and required prolonged washout times before recovery of the muscle. 3 2-Azido-AMP and 2-azidoadenosine were 2 to 12 times more potent than ATP, but took much longer (up to 100 s) to reach maximal relaxation. This behaviour is different from that of AMP and adenosine which were much less potent than ATP. 4 L-Enantiomers of adenosine and adenine nucleotides were also tested. L-ATP and L-ADP were 3 to 6 times less potent than ATP and ADP, and L-AMP and L-adenosine were inactive. 2-Azido-L-ATP and 2-azido-L-ADP were approximately 120 times less potent than 2-Azido-ATP and 6 times less potent than ATP as relaxants of taenia coli. 2-Azido-L-AMP and 2-azidio-L-adenosine were almost inactive. 5 2-Azido derivatives are photolysed by u.v. irradiation to reactive intermediates. 2-Azido-ATP and 2-azidoadenosine might be suitable photoaffinity ligands for labelling putative P2 and P1 purine receptors respectively. 2-Azido-L-ATP and 2-azido-L-adenosine could be useful controls for nonspecific labelling.

Effects of phosphorothioate analogues of ATP, ADP and AMP on guinea-pig taenia coli and urinary bladder.

Phosphorothioate analogues of ATP, ADP and AMP were tested on the guinea-pig taenia coli and urinary bladder. The Rp diastereoisomers of the phosphorothioate analogues, ATP-alpha-S and ADP-alpha-S were respectively 7 and 3 times more effective than the Sp diastereoisomers in causing relaxation of the taenia coli. No stereoselectivity was observed for the diastereoisomers of ATP-beta-S. In guinea-pig bladder, no stereoselectivity was observed for any of the phosphorothioate analogues. These results show that P2-purinoceptors mediating inhibitory responses in the guinea-pig taenia coli show marked stereoselectivity, while P2-purinoceptors mediating excitatory responses in the guinea-pig bladder show little stereoselectivity.

Studies on the stereoselectivity of the P2-purinoceptor on the guinea-pig vas deferens.

ATP, 2-chloro-ATP, 2-methylthio-ATP and their unnatural L-enantiomers, Rp and Sp diastereoisomers of the ATP phosphorothioate analogues, ATP alpha S and ATP beta S, were tested on the guinea-pig vas deferens. The 2-substituted analogues of ATP were no more effective than ATP in causing contraction of the vas deferens. However, stereoselectivity was observed with each pair of enantiomers of ATP, 2-chloro-ATP and 2-methylthio-ATP. No stereoselectivity was observed for the phosphorothioate analogues. Rp- and Sp-ATP beta S were more effective than ATP at eliciting contractions of the vas deferens. These results show that unlike the P2-purinoceptor mediating excitatory responses in the guinea-pig bladder, the P2-purinoceptor mediating contraction in the guinea-pig vas deferens displays stereoselectivity.

Studies on the stereoselectivity of the P2-purinoceptor.

ATP, 2-chloro-ATP, 2-methylthio-ATP, and their unnatural L-enantiomers, were synthesized and their effects tested on the guinea-pig taenia coli and urinary bladder, and the stimulated frog ventricle. The potent P2-purinoceptor agonists, 2-chloro-ATP and 2-methylthio-ATP were, respectively, 30 and 200 times more effective than ATP in relaxing the guinea-pig taenia, but approximately as effective as ATP in contracting the guinea-pig bladder and augmenting the force of contraction of the frog ventricle. A high degree of stereoselectivity was observed for relaxations of the guinea-pig taenia coli produced by the P2-purinoceptoragonists, and 2-methylthio-ATP was over 700 times more effective than its L-enantiomer. In contrast, stereoselectivity for contraction of the guinea-pig bladder was observed only at low concentrations with each pair of enantiomers, and a similar low stereoselectivity was displayed by the frog ventricle. These results show that P2-purinoceptors mediating inhibitory responses in the guinea-pig taenia coli can show a high degree of stereoselectivity, while P2-purinoceptors mediating excitatory responses in the guinea-pig bladder and in the frog ventricle show little stereoselectivity. The partial stereoselectivity of the P2-purinoceptor in smooth muscle contrasts with the absolute stereospecificity of P1-purinoceptors for adenosine on smooth muscle and autonomic nerve terminals and the absolute stereospecificity of the receptor for ADP on the human platelet.

Evidence for stereospecificity of the P1-purinoceptor.

1 The effects of adenosine, 5'-N-ethylcarboxamidoadenosine (NECA), 2-chloroadenosine, 2-azidoadenosine, and their L-enantiomers were examined on driven left atria, trachea and transmurally stimulated ileum of the guinea-pig. 2 In each tissue the order of potency of the D-enantiomers for producing inhibitory effects was NECA greater than 2-chloroadenosine greater than 2-azidoadenosine greater than adenosine. 3 The log concentration-response curve of each agonist was shifted to the right in the presence of the P1-purinoceptor antagonist, theophylline. 4 Dipyridamole, which blocks adenosine uptake, potentiated the effects of adenosine but not those of the D-enantiomers of adenosine analogues. 5 The greater potency of the adenosine analogues therefore, is at least partly due to their resistance to tissue uptake and subsequent enzymatic destruction. 6 The L-enantiomers of adenosine and its analogues did not produce inhibitory responses in the driven left atria or transmurally stimulated ileum. At high concentrations relaxations of the tracheal muscle were obtained, with the potency series L-NECA greater than 2-chloro-L-adenosine greater than 2-azido-L-adenosine greater than L-adenosine. 7 It is concluded that the postsynaptic P1-purinoceptors in the guinea-pig atria and trachea and the presynaptic P1-purinoceptors on cholinergic nerve terminals in guinea-pig ileum are stereospecific for the D-enantiomers of adenosine and its analogues.

Regulation of P2y-purinoceptor-mediated prostacyclin release from human endothelial cells by cytoplasmic calcium concentration.

1. ATP and ATP analogues induced prostacyclin (PGI2) secretion from human cultured umbilical vein endothelial cells. 2. The threshold active concentration for ATP was less than or equal to 1 microM. The rank order of potency of analogues was 2-chloroadenosine 5'-triphosphate (2-ClATP) greater than 2-methylthioadenosine 5'-triphosphate (2-MeSATP) greater than ATP greater than ADP, while adenosine 5'-(alpha,beta-methylene)triphosphonate, AMP and adenosine were inactive, indicating the presence of P2y-purinoceptors. 3. In contrast to their actions on P2y-receptors in guinea-pig taenia coli, isopolar analogues of 2-methylthioadenosine 5'-(beta, gamma-methylene)triphosphonate were less effective than ATP. 4. ATP and ATP analogues increased intracellular free calcium ions, [Ca2+]i, giving a rapid transient peak due predominantly to release from intracellular stores, followed by a maintained steady-state elevated level due to influx. 5. The dose-response curves for peak [Ca2+]i induced by ATP, 2-ClATP and 2-MeSATP were very similar to those for PGI2 production. 6. Elevations of [Ca2+]i, above a threshold value of 0.8-1 microM, were necessary for PGI2 production in response to P2y-receptor activation. 7. The dose relationships between PGI2 release and peak [Ca2+]i were equivalent whether [Ca2+]i was raised by ionomycin or via P2y-receptor activation by ATP or 2-ClATP, indicating that elevations of [Ca2+]i provide the major, if not the exclusive intracellular pathway for P2y-purinoceptor-mediated PGI2 synthesis.

Pharmacological effects of isopolar phosphonate analogues of ATP on P2-purinoceptors in guinea-pig taenia coli and urinary bladder.

Isopolar methylene phosphonate analogues of adenosine triphosphate (ATP) were synthesized and tested on the guinea-pig isolated taenia coli (where ATP causes relaxation) and urinary bladder (where ATP causes contraction), to see if restoration of the electronegativity of the methylene linkage would enhance pharmacological potency. The compounds used were the dichloromethylene and difluoromethylene analogues of adenosine 5'-(beta,gamma-methylene)triphosphonate (AMP-PCP), L-adenosine 5'-(beta,gamma-methylene)triphosphonate (L-AMP-PCP) and 2-methylthioadenosine 5'-(beta,gamma-methylene)-triphosphonate (2-methylthio-AMP-PCP). The order of potency of the analogues depended on the tissue, and was independent of the nature of the purine or ribose moieties. None of the analogues was degraded by ectonucleotidases on either tissue. In the taenia coli the order of potency for relaxation was difluoromethylene greater than or equal to dichloromethylene greater than methylene, and this reflected the order of electronegativity of the analogues. The isopolar analogues of L-AMP-PCP were inactive in the taenia coli. In the bladder the order of potency for contraction was difluoromethylene greater than or equal to methylene greater than dichloromethylene, suggesting that electronegativity is of lesser importance here. The isopolar analogues of L-AMP-PCP were active in this tissue. The differences between the two tissues in the order of potency for these non-degradable analogues supports suggestions that P2-purinoceptors in the taenia coli (P2Y) are different from those in the bladder (P2X). The isopolar analogues of L-AMP-PCP, like L-AMP-PCP itself, were selective agonists at the P2X-purinoceptor.

Subtypes of P2-purinoceptors. Studies using analogues of ATP.

Studies using analogues of ATP have allowed a comparison of structure-activity relationships that has provided ample evidence for the existence of at least four subtypes of P2-purinoceptors responsive to adenine nucleotides. Competitive antagonists have defined clearly the P2T subtype, specific agonists are now available for the P2X and P2Y subtypes, and leads have been given for development of reversible specific antagonists for the P2X and P2Z subtypes. The availability especially of inhibitors of ectonucleotidases and of specific antagonists for each P2-purinoceptor subtype would enable the roles of endogenous extracellular nucleotides to be ascertained, as has already been shown for the interaction of platelets with the vasculature.

Characterisation of the ATP4- receptor that mediates permeabilisation of rat mast cells.

ATP (as the tetrabasic acid, ATP4-) applied externally to rat mast cells causes the formation of lesions which permit influx and efflux of low molecular weight, normally impermeant aqueous solutes. To monitor membrane permeabilisation we have used two fluorescent dyes, ethidium which stains the nucleus, and TMA-DPH which stains the cytosolic surfaces of intracellular membranes following entry into the cells Permeabilisation by ATP is not affected by the metabolic status of the cells, and is maintained at temperatures as low as 8 degrees C. We have tested the ability of 30 structural analogues of ATP to effect mast cell permeabilisation. The analogues include those having substituents in the 2- and 8-positions of the purine ring, structural and optical isomers of the ribose sugar, and variations in the triphosphate chain. The pattern of selectivity displayed by the rat mast cell ATP4- receptor is distinct from those characteristic of the P1 purinoceptor for adenosine and the P2X and P2Y purinoceptors for adenine nucleotides.