Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We showed previously that exposure of cerebellar granule cells to the A1 adenosine receptor (A1AR)-selective agonist, cyclopentyladenosine, decreases A1AR density and G protein coupling corresponding to blunted agonist-induced adenylyl cyclase (EC 4.6.1.1) inhibition. We have now determined that A1AR-mediated adenylyl cyclase inhibition was desensitized in a homologous manner. Carbachol- and baclofen-induced inhibition of adenylyl cyclase was unaffected by 48-h exposure to 10 microM cyclopentyladenosine. Expression of G protein alpha-subunits was not affected dramatically by agonist exposure. The fraction of sequestered A1AR was increased significantly at 4, 24, and 48 h of cyclopentyladenosine exposure (35, 57, and 81% increase over control, respectively). The time course of agonist-induced A1AR sequestration was slower than that reported for other G protein-coupled receptors. Incubation with the adenosine receptor antagonist, 8-p-sulfophenyltheophylline or adenosine deaminase did not alter sequestration significantly. Neither steady-state A1AR mRNA levels nor transcript stability was affected by 48-h agonist exposure. We determined that A1AR half-life in cerebellar granule cells is 20.9 h, which is considerably longer than that reported for several other G protein-coupled receptors. The slow time course of A1AR sequestration and the stability of the corresponding mRNA may be a reflection of the tonic inhibitory tone exerted by adenosine in brain.
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PMID:Cyclopentyladenosine-induced homologous down-regulation of A1 adenosine receptors (A1AR) in intact neurons is accompanied by receptor sequestration but not a reduction in A1AR mRNA expression or G protein alpha-subunit content. 964 69

Experimental evidence in animal models suggests that adenosine is involved in the regulation of digestive functions. This study examines the influence of adenosine on the contractile activity of human colon. Reverse transcription-polymerase chain reaction revealed A(1) and A(2a) receptor expression in colonic neuromuscular layers. Circular muscle preparations were connected to isotonic transducers to determine the effects of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; A(1) receptor antagonist), ZM 241385 (A(2a) receptor antagonist), CCPA (A(1) receptor agonist) and 2-[(p-2-carboxyethyl)-phenethylamino]-5'-N-ethyl-carboxamide-adenosine (CGS 21680; A(2a) receptor agonist) on motor responses evoked by electrical stimulation or carbachol. Electrically evoked contractions were enhanced by DPCPX and ZM 241385, and reduced by CCPA and CGS 21680. Similar effects were observed when colonic preparations were incubated with guanethidine (noradrenergic blocker), L-732,138, GR-159897 and SB-218795 (NK receptor antagonists). However, in the presence of guanethidine, NK receptor antagonists and N(omega)-propyl-L-arginine (NPA; neuronal nitric oxide synthase inhibitor), the effects of DPCPX and CCPA were still evident, while those of ZM 241385 and CGS 21680 no longer occurred. Carbachol-induced contractions were unaffected by A(2a) receptor ligands, but they were enhanced or reduced by DPCPX and CCPA, respectively. When colonic preparations were incubated with guanethidine, NK antagonists and atropine, electrically induced relaxations were partly reduced by ZM 241385 or NPA, but unaffected by DPCPX. Dipyridamole or application of exogenous adenosine reduced electrically and carbachol-evoked contractions, whereas adenosine deaminase enhanced such motor responses. In conclusion, adenosine exerts an inhibitory control on human colonic motility. A(1) receptors mediate direct modulating actions on smooth muscle, whereas A(2a) receptors operate through inhibitory nitrergic nerve pathways.
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PMID:A1 and A2a receptors mediate inhibitory effects of adenosine on the motor activity of human colon. 1901 12