Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.5.4.4 (adenosine deaminase)
5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently shown the presence of adenosine receptors coupled to adenylate cyclase in anterior pituitary and in the present studies we have investigated the effects of adenosine on ACTH release. The 'R'-site specific analogs of adenosine such as N-Ethylcarboxamide adenosine (NECA), L-N6-phenylisopropyl adenosine (PIA), 2-chloro-adenosine (2-Cl-Ado) all stimulated ACTH release in a dose-dependent manner. NECA was the most potent analog and stimulated ACTH release by about 170% with an apparent Ka of 0.1 microM, whereas PIA and 2-Cl-Ado were less potent and stimulated the release by about 110% and 125% with an apparent Ka of 0.2 and 0.4 microM respectively. The stimulation of ACTH release by NECA was inhibited by 3-isobutyl-1-methylxanthine (IBMX). On the other hand, adenosine deaminase (ADA) treatment of the cells also stimulated ACTH release as well as adenylate cyclase activity by about 2-fold, suggesting that endogenous adenosine plays an inhibitory role in the release of ACTH. Other agents, such as corticotropin-releasing factor (CRF), vasoactive intestinal peptide (VIP) and forskolin (FSK) also stimulated ACTH release from these cells. In addition, the stimulation by an optimal concentration of NECA was almost additive with maximal stimulation caused by VIP and FSK. These data suggest that adenosine modulates ACTH release from anterior pituitary through its interaction with adenosine receptors coupled to adenylate cyclase.
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PMID:Adenosine regulates the release of adrenocorticotropic hormone (ACTH) from cultured anterior pituitary cells. 255 Jul 86

1. The effects of several drugs, including antagonists of vasoactive intestinal peptide (VIP), and antisera to VIP or peptide histidine isoleucine (PHI), on relaxation responses of guinea-pig isolated trachea to electrical field stimulation (EFS) have been examined. 2. beta-Adrenoceptor blockade with propranolol only partially blocked the inhibitory response to EFS, but had no effect in tissues from animals pretreated with 6-hydroxydopamine or reserpine. 3. Neither adenosine deaminase, in the presence of dipyridamole, nor the potent adenosine antagonist NPC205 (1,3-n-dipropyl-8-(4-hydroxyphenyl)-xanthine) had any effect on the inhibitory response to EFS. 4. The VIP antagonists, [Ac-Tyr1, D-Phe2]-GRF(1-29)-NH2 and [4-Cl-D-Phe6, Leu17]-VIP had no effect on the inhibitory response to EFS. Moreover, they were without effect on responses to exogenous VIP or PHI. 5. Overnight incubation with VIP antisera markedly reduced the inhibitory response to EFS. PHI antisera had a similar, but smaller effect. 6. In the presence of a concentration of VIP that is maximal for its relaxant effect, inhibitory responses to electrical stimulation were greatly inhibited. 7. Naloxone and reactive blue 2 each had no effect on inhibitory responses indicating that endogenous opioids and adenosine 5'-triphosphate (ATP) respectively are not involved. 8. The results suggest that VIP and PHI, but not adenosine, contribute to non-adrenergic, noncholinergic inhibitory nerve responses of guinea-pig trachea. Moreover, the surprising lack of effect of both VIP antagonists on these responses, and in particular, on responses to exogenous VIP, suggests that the receptors mediating VIP-induced tracheal relaxation are different from those that mediate pancreatic secretion.
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PMID:The effects of vasoactive intestinal peptide (VIP) antagonists, and VIP and peptide histidine isoleucine antisera on non-adrenergic, non-cholinergic relaxations of tracheal smooth muscle. 272 Feb 90

We examined the mechanism by which adenosine inhibits prolactin secretion from GH3 cells, a rat pituitary tumour line. Prolactin release is enhanced by vasoactive intestinal peptide (VIP), which increases cyclic AMP, and by thyrotropin-releasing hormone (TRH), which increases inositol phosphates (IPx). Analogues of adenosine decreased prolactin release, VIP-stimulated cyclic AMP accumulation and TRH-stimulated inositol phospholipid hydrolysis and IPx generation. Inhibition of InsP3 production by R-N6-phenylisopropyladenosine (R-PIA) was rapid (15 s) and was not affected by the addition of forskolin or the removal of external Ca2+. Addition of adenosine deaminase or the potent adenosine-receptor antagonist, BW-A1433U, enhanced the accumulation of cyclic AMP by VIP, indicating that endogenously produced adenosine tonically inhibits adenylate cyclase. The potency order of adenosine analogues for inhibition of cyclic AMP and IPx responses (measured in the presence of adenosine deaminase) was N6-cyclopentyladenosine greater than R-PIA greater than 5'-N-ethylcarboxamidoadenosine. This rank order indicates that inhibitions of both cyclic AMP and InsP3 production are mediated by adenosine A1 receptors. Responses to R-PIA were blocked by BW-A1433U (1 microM) or by pretreatment of cells with pertussis toxin. A greater amount of toxin was required to eliminate the effect of R-PIA on inositol phosphate than on cyclic AMP accumulation. These data indicate that adenosine, in addition to inhibiting cyclic AMP accumulation, decreases IPx production in GH3 cells, possibly by directly inhibiting phosphoinositide hydrolysis.
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PMID:Regulation of GH3-cell function via adenosine A1 receptors. Inhibition of prolactin release, cyclic AMP production and inositol phosphate generation. 284 12

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

Patients with tumors secreting vasoactive intestinal peptide (VIP) often develop hyperglycemia and glucose intolerance. Although VIP has been reported to increase glucose output by the liver, the concentration required for this effect greatly exceeds that observed clinically. We therefore investigated the effects of VIP on insulin-stimulated glucose transport in isolated adipocytes. Inhibition of insulin action was observed at a concentration of 1 ng/ml VIP with half-maximal inhibition at approximately 20 ng/ml. 125I-VIP bound to specific high-affinity sites on the adipocytes. Fifty percent inhibition of binding occurred at a concentration of unlabeled VIP of approximately 10 ng/ml and was not affected by insulin, glucagon, or growth hormone. As we have observed previously with glucagon and catecholamines, inhibition of insulin action by VIP was observed only when accumulation of adenosine in the incubation medium was prevented by addition of adenosine deaminase. Under these conditions VIP markedly increased cellular cAMP levels. A good correlation was observed among VIP binding, inhibition of insulin-stimulated glucose transport, and cellular concentrations of cAMP. The results suggest that inhibition of insulin action in adipose tissue contributes to the hyperglycemic effect of VIP. Together, with our published findings on glucagon and catecholamines, these results support the hypothesis that counterregulatory hormones inhibit insulin action by increasing cellular concentrations of cAMP.
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PMID:Vasoactive intestinal peptide inhibits insulin-stimulated glucose transport in rat adipocytes. 300 79

Two main candidates, adenosine 5'-triphosphate (ATP) and vasoactive intestinal peptide (VIP), have been proposed as inhibitory transmitters at neuromuscular junctions in the gut. We have used a photoaffinity analogue of ATP, 3'-O-(4-benzoyl)benzoyl ATP or BzATP, that binds covalently to ATP receptors and inactivates them in the presence of light and a specific high-affinity VIP antiserum in order to examine the contributions of ATP and VIP to neurally induced relaxation in circular smooth muscle of the gastric fundus of the guinea pig. VIP and ATP caused dose-dependent relaxation; the effect of ATP was equal to that of its stable isostere, alpha, beta-methylene ATP, and was resistant to degradation by adenosine deaminase, indicating interaction of ATP with purinergic P2-receptors. Relaxation induced by VIP was selectively inhibited by VIP antiserum (final dilution 1:120), while that induced by ATP was selectively inhibited by photoactivated BzATP. Relaxation induced by electrical field (i.e., neural) stimulation was inhibited by VIP antiserum only; photoactivated BzATP had no effect. Inhibition of neurally induced relaxation ranged from 86% (P less than 0.01) at the lowest frequencies to 34% (P less than 0.01) at the highest frequencies. Maximal field stimulation caused an 11-fold increase in VIP release from intramural neurons. The results strongly favor VIP as the neural mediator of gastric relaxation.
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PMID:Vasoactive intestinal peptide as a neural mediator of gastric relaxation. 396 63

Although secretin and vasoactive intestinal peptide (VIP) stimulate production of the second-messenger substance cyclic AMP and exert a positive inotropic action on rat ventricle in vitro, a direct action of these peptides on cardiomyocytes has not been established. In contrast to hearts of other mammalian species, which possess VIP-preferring receptors, rat heart is unique in that the existence of a "relatively nonselective receptor" at which both secretin and VIP may bind has been proposed. We wished to define the receptor(s) for secretin and VIP present on rat ventricular cardiomyocytes using a homogeneous suspension of viable cells. With adenosine deaminase 5 U/ml and the phosphodiesterase (PDE) inhibitor isobutyl methylxanthine (IBMX) 1 mM, both secretin and VIP increased intracellular levels of cyclic AMP maximally and concentration dependently after 5 min: EC50 values were 8 and 58 nM, respectively. At maximally effective concentrations, secretin 1 microM increased intracellular levels of cyclic AMP fourfold above basal levels, whereas a 1.6-fold increase was induced by VIP 10 microM. Maximum changes in cell length (dL) of isolated cardiomyocytes during electrically stimulated (0.5 Hz) contractions were determined in the presence of adenosine deaminase 2.5 U/ml. Under these conditions, both secretin and VIP produced a concentration-dependent positive contractile response that became maximal 5 min after addition of the peptide. Secretin 50 nM increased the amplitude of cellular contractions maximally to a value 37% greater than that obtained without peptide. VIP 20 nM increased the amplitude of cellular contractions maximally to a value 19% greater than that obtained without peptide. The EC50 values were 470 and 700 pM for VIP and secretin, respectively. The selective antagonist at VIP-preferring receptors, 4-Cl DPhe-6 Leu-17 VIP 10 microM did not antagonise the actions of VIP. In the presence of the selective antagonist at receptors for secretin, secretin 7-27 > or = 10 microM, the concentration dependence of the effect of secretin on accumulation of cellular cyclic AMP and contractile amplitude displayed a rightward parallel shift: the pA2 value for secretin 7-27 was 4.96. Secretin 7-27 also induced a rightward parallel shift of the concentration dependence of the actions of VIP. VIP 10 microM was additive with low concentrations of secretin (< 10 nM) in stimulating production of cyclic AMP but antagonised this response at higher concentrations of secretin (> 10 nM). Similarly, VIP 2 and 20 nM enhanced the contractile response to low concentrations of secretin (< 1 nM), but antagonised the response at higher concentrations of secretin (> 1 nM).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Secretin and vasoactive intestinal peptide are potent stimulants of cellular contraction and accumulation of cyclic AMP in rat ventricular cardiomyocytes. 752 89

Secretin, vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) each exert potent positive contractile responses directly in rat ventricular cardiomyocytes. However, the contractile-coupling mechanisms associated with these responses have not been determined. In the present study, the involvement of L-type calcium channels in the contractile responses elicited by each peptide has been investigated using the selective antagonists at L-type calcium channels, verapamil and diltiazem. Ventricular cardiomyocytes, isolated from the hearts of adult rats, were stimulated to contract at 0.5 Hz in the presence of CaCl2 (2 mM) and adenosine deaminase (5U/ml). Cardiomyocytes were pre-incubated for 3 min prior to stimulation, in the absence of L-type calcium channel antagonist, and in the presence of verapamil (< or = 1 microM) or diltiazem (< or = 1 microM). Verapamil (< or = 1 microM) and diltiazem (< or = 1 microM) inhibited the contractile responses elicited by isoprenaline (100 nM) and forskolin (40 microM), used as positive controls, significantly, and in a concentration-dependent manner, but did not inhibit significantly the contractile response elicited by phenylephrine (2 microM), which was employed as a negative control. Verapamil (< or = 1 microM) and diltiazem (< or = 1 microM) inhibited the contractile responses to secretin (20 nM) and VIP (20 nM) significantly, and in a concentration-dependent manner, but did not inhibit the contractile response to CGRP. These data indicate that the positive contractile responses to secretin and VIP in mammalian ventricular cardiomyocytes involve the influx of calcium ion via L-type calcium channels, while the positive contractile response to CGRP does not.
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PMID:Inhibition by verapamil and diltiazem of agonist-stimulated contractile responses in mammalian ventricular cardiomyocytes. 852 57

The effects of group 2- versus group 3-selective metabotropic glutamate (mGlu) receptor agonists were examined against forskolin (10 microM)-, vasoactive intestinal peptide (VIP; 1 microM)- and 5'-N-ethylcarboxamidoadenosine (NECA; 10 microM)-stimulated cAMP accumulations in adult rat hippocampal slices (in the presence of adenosine deaminase). Group 2 mGlu receptor-selective ((1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic acid (1S,3R-ACPD) and (2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine (L-CCG I)) and group 3 mGlu receptor-selective (L-2-amino-4-phosphonobutyric acid (L-AP4) and L-serine-O-phosphate) agonists greatly inhibited forskolin-stimulated cAMP formation ( > 80% at maximally effective concentrations). In contrast, stimulation of cAMP by VIP or NECA was inhibited by group 3, but not by group 2, mGlu receptor agonists. In fact, group 2 mGlu receptor agonists greatly potentiated cAMP accumulation evoked by NECA. Both the inhibitory effects of 1S,3R-ACPD on forskolin-stimulated cAMP and the potentiating effects on NECA-stimulated cAMP accumulation were reversed by the competitive group 1/2 mGlu receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG). However, (+)-MCPG had no effects on L-AP4 inhibition of cAMP. Thus, the effects of group 2 versus group 3 mGlu receptor agonists on cAMP coupling can be pharmacologically as well as functionally differentiated in the rat hippocampus.
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PMID:Differentiation of group 2 and group 3 metabotropic glutamate receptor cAMP responses in the rat hippocampus. 866 60

The effect of vasoactive intestinal peptide (VIP) on evoked [(3)H]-acetylcholine ([(3)H]-ACh) release from motor nerve terminals, and its interaction with presynaptic facilitatory A(2A)-adenosine receptors was investigated in the rat phrenic nerve-hemidiaphragms. Facilitation of [(3)H]-ACh release by VIP (100 nM) only becomes apparent when high frequency (50 Hz) or long lasting pulses (1 ms) were delivered to the phrenic nerve; VIP excitation was prevented by removal of endogenous adenosine tonus, with adenosine deaminase (2.5 units/ml) or with the A(2A)-receptor antagonist, 3,7-dimethyl-1-propargyl xanthine, (10 microM). Pretreatment with the selective A(2A)-receptor agonist, CGS 21680C (2 nM), potentiated the neurofacilitatory action of VIP (100 nM). The results suggest that tonic A(2A)-receptors activation by endogenous adenosine is required to trigger the facilitatory action of VIP on evoked [(3)H]-ACh release from motor nerve endings.
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PMID:Synergism between A(2A)-adenosine receptor activation and vasoactive intestinal peptide to facilitate [3H]-acetylcholine release from the rat motor nerve terminals. 1150 55


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