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)

Two main candidates have been proposed for the role of relaxant neurotransmitter in the intestine: (a) the purine nucleotide, 5'-adenosine triphosphate (ATP) and (b) the neuropeptide, vasoactive intestinal peptide (VIP). The candidacy of VIP is favored by its precise location in nerve fibers that innervate circular smooth muscle and tenia coli. We have used a photoaffinity analog of ATP, 3'-O-(4-Benzoyl)benzoyl ATP, that binds irreversibly to ATP receptors and inactivates them in the presence of light, and a specific VIP antiserum to examine the claims of VIP and ATP as relaxant neurotransmitters in tenia coli of the guinea pig. Both VIP and ATP caused dose-dependent, tetrodotoxin-insensitive relaxation of tenia coli. The effect of ATP was equipotent to that of its stable isostere alpha, beta-methylene ATP and resistant to degradation by adenosine deaminase, indicating interaction of ATP with purinergic-P2 receptors. Photoactivated 3'-O-(4-Benzoyl) benzoyl adenosine triphosphate selectively inhibited relaxation induced by ATP but had no effect on relaxation induced by VIP or by field (i.e., neural) stimulation. Vasoactive intestinal peptide antiserum (final dilution 1:60), on the other hand, inhibited relaxation caused by VIP and by field stimulation but had no effect on relaxation caused by ATP. Neither normal rabbit serum nor preneutralized VIP antiserum had any effect on relaxation induced by ATP, VIP, or field stimulation. Inhibition of neurally induced relaxation by VIP antiserum ranged from 52% +/- 7% (p less than 0.01) at the lowest frequency of stimulation to 15% +/- 4% (p less than 0.01) at the highest frequency, consistent with competitive interaction between antiserum and neurally released VIP. Near-maximal field stimulation at 1 Hz caused an eightfold (800% +/- 49%, p less than 0.01) increase in VIP release into the bathing medium. The results favor VIP (and probably peptide histidine isoleucine, a relaxant homologue known to be cosynthesized with VIP) as the main neural mediator of relaxation in tenia coli.
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PMID:Vasoactive intestinal peptide. Relaxant neurotransmitter in tenia coli of the guinea pig. 286 Nov 38

Vasoactive intestinal peptide (VIP) modulates GABA release from hippocampal nerve terminals and enhances hippocampal synaptic transmission through a pathway dependent on GABAergic transmission. Since VIP modulation of hippocampal synaptic transmission is dependent on the tonic actions of adenosine we investigated if endogenous adenosine could influence VIP enhancement of GABA release from isolated hippocampal nerve endings, and which adenosine receptors could be mediating this influence. When extracellular endogenous adenosine was removed using adenosine deaminase (ADA, 1U/ml), the enhancement (57.2+/-3.7%) caused by VIP on GABA release was prevented. Blockade of adenosine A(1) receptors with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10nM) or of A(2A) receptors with ZM241385 (50nM) abolished the effect of VIP. In the presence of ADA, selective A(2A) receptor-activation with CGS21680 (10nM) readmitted most of the enhancement caused by VIP on GABA release (50.7+/-5.3%). Also in the presence of ADA, A(1) receptor activation with N(6)-cyclopentyladenosine (CPA, 50nM) partially readmitted that effect of VIP (32.6+/-3.8%). In conclusion, the enhancement of GABA release caused by VIP in hippocampal nerve terminals is dependent on the tonic actions of adenosine on both A(1) and A(2A) receptors, and this action of adenosine is essential to VIP modulation of GABA release.
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PMID:A1 and A2A receptor activation by endogenous adenosine is required for VIP enhancement of K+ -evoked [3H]-GABA release from rat hippocampal nerve terminals. 1805 36