alpha,beta-Methyleneadenosine 5'-triphosphate trisodium salt

Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant irritable bowel syndrome.[Pubmed:29456408]

World J Gastroenterol. 2018 Feb 14;24(6):693-705.

AIM: To elucidate the mechanism of patchouli alcohol (PA) in treatment of rat models of diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: We studied the effects of PA on colonic spontaneous motility using its cumulative log concentration (3 x 10(-7) mol/L to 1 x 10(-4) mol/L). We then determined the responses of the proximal and distal colon segments of rats to the following stimuli: (1) carbachol (1 x 10(-9) mol/L to 1 x 10(-5) mol/L); (2) neurotransmitter antagonists including N(omega)-nitro-L-arginine methyl ester hydrochloride (10 mumol/L) and (1R*, 2S*)-4-[2-Iodo-6-(methylamino)-9H-purin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexan e-1-methanol dihydrogen phosphate ester tetraammonium salt (1 mumol/L); (3) agonist alpha,beta-methyleneadenosine 5'-triphosphate trisodium salt (100 mumol/L); and (4) single KCl doses (120 mmol/L). The effects of blockers against antagonist responses were also assessed by pretreatment with PA (100 mumol/L) for 1 min. Electrical-field stimulation (40 V, 2-30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe nonadrenergic, noncholinergic neurotransmitter release in IBS-D rat colon. The ATP level of Kreb's solution was also determined. RESULTS: PA exerted a concentration-dependent inhibitory effect on the spontaneous contraction of the colonic longitudinal smooth muscle, and the half maximal effective concentration (EC50) was 41.9 mumol/L. In comparison with the KCl-treated IBS-D group, the contractile response (mg contractions) in the PA + KCl-treated IBS-D group (11.87 +/- 3.34) was significantly decreased in the peak tension (P < 0.01). Compared with CCh-treated IBS-D rat colon, the cholinergic contractile response of IBS-D rat colonic smooth muscle (EC50 = 0.94 mumol/L) was significantly decreased by PA (EC50 = 37.43 mumol/L) (P < 0.05). Lack of nitrergic neurotransmitter release in stress-induced IBS-D rats showed contraction effects on colonic smooth muscle. Pretreatment with PA resulted in inhibitory effect on L-NAME-induced (10 mumol/L) contraction (P < 0.05). ATP might not be the main neurotransmitter involved in inhibitory effects of PA in the colonic relaxation of stress-induced IBS-D rats. CONCLUSION: PA application may serve as a new therapeutic approach for IBS-D.

Is there a basis for distinguishing two types of P2-purinoceptor?[Pubmed:2996968]

Gen Pharmacol. 1985;16(5):433-40.

It is suggested that the P2-purinoceptor may be separated into two subtypes largely on the basis of the rank order of agonist potency of structural analogues of ATP and also on the activity of antagonists at the P2-purinoceptor: Subtype 1 (designated P2X), potency order: alpha, beta-methyleneATP, beta, gamma-methyleneATP greater than ATP = 2 methylthioATP; antagonism by ANAPP3 and selectively desensitisation following administration of alpha, beta-methyleneATP; present in the vas deferens and urinary bladder of guinea-pig and rat, frog and rat ventricle, and also in the smooth muscle of the rat femoral artery and rabbit central ear artery, where they mediate excitation. Subtype 2 (designated P2Y), potency order: 2-methylthioATP much greater than ATP greater than alpha, beta-methyleneATP, beta, gamma-methyleneATP; weak antagonism by ANAPP3 and desensitisation following administration of alpha, beta-methyleneATP; present in the guinea-pig taenia coli and the longitudinal muscle layer of the rabbit portal vein, where they mediate relaxation and also on the vascular endothelial cells of the rat femoral artery and pig aorta (where occupation leads to the production of endothelium-derived relaxing factor). Differences in the structure of the P2-purinoceptor in various tissues may be useful in the development of drugs for the treatment of vascular, gastrointestinal and urinoglenital disorders.