Investigation of the selectivity of α, β‐methylene ATP in inhibiting vascular responses of the rat in vivo and in vitro

Abstract

1 The proposal that a,fi-methylene adenosine 5'-triphosphate (mATP) inhibits pressor responses in the pithed rat by selective desensitization of P2.-purinoceptors was examined by comparing the selectivity of its inhibitory effect on vascular responses in vitro and in vivo.2 In isolated ring preparations of rat femoral and tail artery, which had been denuded of endothelium, mATP markedly reduced the contractile response to exogenous ATP but had no effect on the response of the arteries to exogenous noradrenaline (NA). 3 In the pithed rat a substantial proportion of the pressor response to sympathetic nerve stimulation was resistant to a-adrenoceptor blockade, suggesting a non-adrenergic component to the sympathetic vasoconstriction. 4 In the pithed rat, repeated administration of desensitizing doses of mATP attenuated the pressor response to sympathetic nerve stimulation by approximately 80%, suggesting that a component of the sympathetic vasoconstriction is mediated by ATP acting on vascular P21-purinoceptors. However, the same mATP treatment also attenuated, to a similar degree, the pressor responses to intravenous NA, angiotensin II and vasopressin, indicating that the desensitization procedure was non-selective.5 These results demonstrate that while mATP can be used to desensitize selectively P2.-purinoceptors in vitro, its attenuation of the sympathetic nerve-mediated pressor response in vivo is non-selective.

The dual nature of extracellular ATP as a concentration-dependent platelet P2X1 agonist and antagonist

“…29,44 Moreover, MeATP is also known to ''desensitize'' the platelet P2X1 receptor, thereby decreasing the overall Ca 2+ influx into the platelet. 45 Fig. 4 Concentration-dependent dual nature of ATP as a platelet antagonist and agonist.…”

Both Extracellular Atp and Shear Stress Regulate the Release of Nitric Oxide in Rat Caudal Artery

“…Extracellular ATP is known to have a number of biological and pharmacological effects in blood vessels by acting on specific cell‐surface P 2 purinoceptors located on vascular smooth muscles 34 . In the rat caudal artery, ATP produced a vasoconstriction by acting on P 2X purinoceptors, an action that has been observed at higher concentrations of ATP (more than 100 μmol/L) 35 –37 . Although it is not possible to calculate from the present data the exact concentration of endogenous ATP released from the caudal artery that is then available to interact with tissue‐specific purinoceptors, a reasonable approximation of the amount of ATP per tissue volume can be made and is approximately 300 nmol/L.…”

“…34 In the rat caudal artery, ATP produced a vasoconstriction by acting on P2X purinoceptors, an action that has been observed at higher concentrations of ATP (more than 100 µmol/L). [35][36][37] Although it is not possible to calculate from the present data the exact concentration of endogenous ATP released from the caudal artery that is then available to interact with tissue-specific purinoceptors, a reasonable approximation of the amount of ATP per tissue volume can be made and is approximately 300 nmol/L. This value is rather close to the concentration of ATP (500 nmol/L) that was observed to increase intracellular Ca 2ϩ levels, 33 but did not produce a direct response of the smooth muscle.…”

Nucleotides as Cotransmitters in Vascular Sympathetic Neuroeffector Transmission

“…Data from Weitzell et al [13], stimulation in rat tail arteries persisted in the presence of phentolamine but were abol ished after desensitization of purine P^x re ceptors [6] by a,p-methylene-ATP. Analo gous evidence for the mechanical response followed: a,P-methylene-ATP abolished the a-adrenoceptor-antagonist-resistant neuro genic constriction of branches of the rabbit isolated ileocolic artery [7] and also reduced sympathetic vasopressor responses in pithed rats [8], although the selectivity of the desen sitization by a,p-methylene-ATP in whole animal preparations is in doubt [9,10], We summarize here our evidence for NA-ATP cotransmission in isolated blood vessels from rabbits. Attention was also paid to pre junctional 012-autoinhibition [11,12] in co transmission systems.…”