Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0848283 (rundown)
 502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of prejunctional purinoceptors (P1-subtype) in the control of ATP-release from inhibitory motoneurons was investigated electrophysiologically, by studying fast purinergic inhibitory junction potentials (IJPs) in guinea-pig ileal circular muscle. Pressure ejections of adenosine and ATP (but not of alpha,beta-methylene ATP) onto circular muscle depressed the amplitude of fast IJPs, indicating the presence of prejunctional P1-purinoceptors. An adenosine (A1/2)-receptor antagonist, theophylline (10(-8)-10(-4) M), increased the amplitude of fast IJPs in a dose-related manner (EC50 = 17.5 microM), suggesting the existence of a basal 'adenosine tone' that regulated ATP-release from ileal motoneurons. However, three methylxanthine derivatives, caffeine (10(-8)-10(-4) M), 3-isobutyl-1-methylxanthine (IBMX; 10(-8)-10(-4) M) and the potent A1-receptor antagonist 1,3-dipropyl-8-(2-amino-4-chlorophenyl)-xanthine (DPCPX; 10(-8)-10(-4) M), failed to potentiate fast IJPs and placed in doubt the existence of this inhibitory adenosine tone. Caffeine and IBMX, but not DCPCX, hyperpolarised ileal circular muscle in a dose-related manner and reduced IJP-amplitude; DPCPX did not alter the amplitude of IJPs. The non-specific inhibitor of phosphodiesterases, Ro-20-1724 (5 x 10(-7)-5 x 10(-5) M), increased the amplitude of fast IJPs, mimicking the actions of theophylline. To this extent, facilitation of inhibitory transmission appeared to involve phosphodiesterase inhibition and modification of intra-axonal cAMP levels and phosphorylation of intra-axonal protein kinases. The phenomenon of IJP rundown, presumed to be a manifestation of prejunctional autoinhibition, was studied using theophylline and DPCPX as A1-receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prejunctional autoinhibition of purinergic transmission in circular muscle of guinea-pig ileum; a mechanism distinct from P1-purinoceptor activation. 802 18

1 Ca2+ imaging was used to investigate interactions between responses induced by N-methyl-D-aspartate (NMDA; 15 microm) and (RS)-3,5-dihydroxyphenyl-glycine (DHPG; 30 microm) in human embryonic kidney (HEK) 293 cells, transiently transfected with rat recombinant NR1a, NR2A and mGlu5a cDNA. 2 Responses to NMDA were reversibly depressed by DHPG from 244+/-14 to 194+/-12% of baseline. Treatment with thapsigargin (1 microm, 10 min) prevented this effect. 3 After thapsigargin pretreatment, repeated applications of NMDA showed a gradual rundown in amplitude over a period of several hours, and were unaffected by DHPG. 4 Continuous perfusion with staurosporine (0.1 microm), after thapsigargin pretreatment, converted the run-down to a small increase in NMDA responses to 123+/-6 % of baseline. DHPG induced a further and sustained potentiation of NMDA responses to 174+/-12% of the initial baseline. 5 The protein tyrosine kinase (PTK) inhibitors genistein (50 microm) and 3-(4-chlorophenyl)1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (PP2; 1 microm) inhibited the staurosporine- and DHPG-induced potentiation of NMDA responses. 6 The protein phosphatase (PTP) inhibitors orthovanadate (100 microm) and phenyl arsine oxide (PAO, 1 microm) facilitated the staurosporine-evoked potentiation of NMDA responses and occluded DHPG-induced potentiation. 7 In conclusion, complex interactions can be demonstrated between mGlu5 and NMDA receptors expressed in HEK293 cells. There is a negative inhibitory influence of Ca2+ release and PKC activation. Inhibition of these processes reveals a tonic, mGlu5 receptor and PTK-dependent potentiation of NMDA receptors that can be augmented by either stimulating mGlu5 receptors or by inhibiting PTPs.
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PMID:Interactions between NMDA receptors and mGlu5 receptors expressed in HEK293 cells. 1521 May 75