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The presence of several subtypes of P2X receptors on early hemopoietic precursors (CD34+) from human umbilical blood was detected by flow cytometry. The expression of P2X receptors on umbilical blood lymphocytes was an order of magnitude higher than that on adult human blood cells. Our results attest to early involvement of P2X receptors in differentiation of human hemopoietic cells.

The ability of 12 new thiazole derivatives to influence the muscle contractility mediated by purine P2X receptors has been studied in vitro using isolated tissues of rats and guinea pigs. Most of the synthesized compounds did not cause significant effects, but two compounds exhibited pronounced antagonism with respect to P2X-mediated contractility response. These compounds offer a good starting point for the synthesis of new effective antagonists of P2 receptors.

In women with various gynecological disorders, ATP, ADP, and 2-methylthio-ATP dose-dependently potentiated spontaneous contractility of isolated fallopian tubes, while alpha,beta-methylene-ATP and uridine triphosphate were little efficient. Pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid, a P2-receptor antagonist, inhibited responses to 2-methylthio-ATP, produced no effect on responses to ATP, and potentiated ADP-induced responses in fallopian tubes. During inflammation, sensitivity of fallopian tubes to P2 agonists and antagonists decreased. The data attest to the presence of functionally active P2 receptors in human fallopian tubes probably involved in the regulation of their mechanical activity.

Experiments on rats showed that pulse therapy with prednisolone (100 mg/kg intraperitoneally for 3 days) stimulated urinary excretion of hydroxyproline, increased the content of inorganic phosphorus, promoted the increase in the content of dienic conjugates and catalase activity, and decreased serum levels of MDA and ceruloplasmin. Ten-day treatment with dimephosphone (208 mg/kg) or xydiphone (45 mg/kg) after pulse therapy with prednisolone normalized urinary excretion of hydroxyproline and reduced the levels of dienic conjugates. Dimephosphone did not change, while xydiphone normalized the level of MDA decreased by prednisolone.

Here we review the results of physiological, pharmacological, and pathophysiological studies of ATP receptors, P2 type receptors. Characteristics of two families of P2 receptors (P2X and P2Y) are presented and the possibility of using preparations affecting these receptors is discussed.

We studied the effects of adenosine and ATP on contractile function of the isolated strip from mouse diaphragm. ATP significantly increased the strength of muscle contraction induced by carbachol. Adenosine had no effect on carbachol-induced muscle contraction. P2 receptor antagonist suramin abolished the effect of ATP. The positive chronotropic effect of ATP was not observed after treatment with specific protein kinase C inhibitor chelerythrine. Our results indicate that the effect of ATP on contractile function of mouse diaphragm is realized via protein kinase C.

ATP-induced inflammation was investigated using subplantar injection in the mouse hind paw. The order of efficacy of purinoceptor agonists for inducing paw oedema (30 nmol per paw) was ATP = alpha, beta-methylene ATP = 2-methylthio ATPadenosineUTPADPAMP. Diadenosine polyphosphates effectively induced paw oedema formation with an order of efficacy of: P1,P4-di(adenosine-5')tetraphosphate = P1,P5-di(adenosine-5')-pentaphosphate = P1,P6-di(adenosine-5')hexaphosphateATP = P1,P3-di(adenosine-5')triphosphateP1,P2-di(adenosine-5')pyrophosphate. Systemic administration of P2-purinoceptor antagonists (30-100 mu mol/kg), suramin, 4,4'-diisothiocyanatostilbene-2,2'-disulphonate, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid and cibacron blue, reduced the intensity of ATP-induced oedema. At 30 mu mol/kg 8-(p-sulfophenyl)theophylline (non-selective adenosine receptor antagonist), 3,7-dimethyl-1,1-propargylxanthine (adenosine A2 receptor antagonist), triprolidine (histamine H1 receptor antagonist), ranitidine (histamine H2 receptor antagonist) and ketanserin (5-hydroxytryptamine 5-HT2 receptor antagonist), but neither 8-cyclopentyl-1,3-dipropylxanthine (adenosine A1 receptor antagonist), nor indomethacin (cyclooxygenase inhibitor) inhibited the ATP-induced swelling. Topical (100 nmol per paw), but not systemic (100 mu mol/kg) administration of NG-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor) reduced the intensity of the ATP-induced paw oedema. These results show that ATP can induce an inflammatory oedematous reaction and contribute to our understanding of the underlying mechanisms.

In vitro experiments were carried out to measure the contractile responses to P2-receptor agonists in the greater saphenous vein isolated from patients with obliterating vascular atherosclerosis and varicose veins of the legs. In patients with varicose veins, the contractile responses of the greater saphenous vein to ATP, α,β-methylene-ATP, and UTP were significantly lower than in patients with obliterating atherosclerosis, while the responses to ADP, adenosine, and 2-methylthio-ATP were similar in both groups. These data attest to the presence of P2-receptor-mediated contraction component in the greater saphenous vein, which are pronouncedly weakened during varicose disease.

We studied contractile responses of isolated smooth muscles from human uterus induced by P2 receptor agonists. In preparations from pregnant uterus all tested P2 receptor agonists caused smooth muscle contractions. The relative activity of P2 receptor agonists decreased in the following order: a,b-methylene-ATP-uridine triphosphate-ATP. Responses induced by ATP and ADP were similar. The amplitude of contractions induced by alpha,beta-methylene-ATP significantly decreased in the presence of P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid. None of tested P2 receptor agonists induced contractions of isolated myometrium from nonpregnant women. Our results indicate that pregnant human uterus contains P2 receptors mediating the contractile response.

Contractile activity of the isolated myometrium from pregnant women with mycoplasma, chlamydial, and mixed mycoplasma-chlamydial infections of the urogenital system was studied in vitro by pharmacological methods. The amplitude of uterine contractions induced by oxytocin and prostaglandin F2a decreased in women with mycoplasma infection, but increased during chlamydial and mixed infections. These data can help to predict pregnancy complications in women with specific urogenital infections.

In vitro experiments showed that P2X-receptor agonist α,β-methylene-ATP and electrical field stimulation in the presence of muscarinic and α-adrenoreceptors blockers induced contractile responses of isolated guinea pig bladder, which were more pronounced at 30°C than at 37°C or 42°C. P2X-receptor antagonist pyridoxal-6-phosphate-2',4'-disulfonic acid, produced a more potent inhibitory effect on contractions induced by electrical field stimulation at 30°C in comparison with that at 37°C or 42°C, while the contractions induced by α,β-methylene-ATP were similarly suppressed at all examined temperatures.

High-performance liquid chromatography and colorimetry of inorganic phosphorus show that in the presence of muscle tissues from the guinea pig bladder, seminal duct, small intestine, longitudinal cord of the cecum, and right atrium all diadenosine polyphosphates with a common formula APnA (n=2–6) are degraded more slowly than ATP. The rate of APnA cleavage is highest in experiments with the small intestinal and right atrial tissues. P2-purine receptor antagonist suramin inhibits degradation of AP3A by right atrial tissue and does not modify degradation of other APnA. Enzymatic stability of endogenous APnA is apparently the principal condition for manifestation of their biological effects.