scholarly journals Role of S-adenosylhomocysteine hydrolase in adenosine metabolism in mammalian heart

1981 ◽  
Vol 196 (1) ◽  
pp. 65-70 ◽  
Author(s):  
J Schrader ◽  
W Schütz ◽  
H Bardenheuer
Keyword(s):  
Guinea Pig ◽  
Adenosine Deaminase ◽  
Myocardial Cell ◽  
Homocysteine Thiolactone ◽  
Adenosylhomocysteine Hydrolase ◽  
Endogenous Adenosine ◽  
Adenosine Transport ◽  
Tissue Contents ◽  
Intact Heart

S-Adenosylhomocysteine hydrolase of mammalian hearts from different species is exclusively a cytosolic enzyme. The apparent Km for the guinea-pig enzyme was 2.9 microM (synthesis) and 0.39 microM (hydrolysis). Perfusion of isolated guinea-pig hearts for 120 min with L-homocysteine thiolactone (0.23 mM) and adenosine (0.1 mM), in the presence of erythro-9-(2-hydroxynon-3-yl)adenine to inhibit adenosine deaminase, caused tissue contents of S-adenosylhomocysteine to increase from 3.5 to 3600 nmol/g. When endogenous adenosine production was accelerated by perfusion of hearts with hypoxic medium (30% O2), L-homocysteine thiolactone (0.23 mM) increased S-adenosyl-homocysteine 17-fold to 64.3 nmol/g within 15 min. In the presence of 4-nitro-benzylthioinosine (5 microM), an inhibitor of adenosine transport, S-adenosylhomocysteine further increased to 150 nmol/g. L-Homocysteine thiolactone decreased the hypoxia-induced augmentation of adenosine, inosine and hypoxanthine in the tissue and the release of these purines into the coronary system by more than 50%. Our findings indicate that L-homocysteine can profoundly alter adenosine metabolism in the intact heart by conversion of adenosine into S-adenosylhomocysteine. Adenosine formed during hypoxia was most probably generated within the myocardial cell.

Studies on a modulatory role for adenosine in antigen and arachidonic acid induced contractions of guinea pig airways

1986 ◽  
Vol 64 (3) ◽  
pp. 225-230 ◽  
Author(s):  
John F. Burka
Keyword(s):  
Arachidonic Acid ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Effective Inhibitor ◽  
Weak Effect ◽  
Endogenous Adenosine ◽  
Transport Inhibitor ◽  
Adenosine Transport ◽  
Adenosine Derivatives

The modulatory effects of adenosine and selected derivatives were examined on antigen and arachidonic acid (AA) induced contractions of indomethacin-treated tracheal spirals and lung parenchymal strips from actively sensitized guinea pigs. Adenosine (up to 2 × 10−4 M) had no effect on antigen-induced contractions, but inhibited AA-induced contractions by 30–40% if added 30 min prior to challenge. The weak effect of adenosine suggests that endogenous adenosine may only have a limited modulatory role in allergic bronchospasm. 2-Chloroadenosine (10−6–10−4 M) dose-dependently inhibited antigen- and AA-induced contractions of trachea, but was considerably less effective on parenchyma. The substituted adenosine derivatives, R-phenylisopropyladenosine (R-PIA) and 5′-(N-ethylcarboxamido)-adenosine (NECA), and the adenosine transport inhibitor, 6-[p-nitrobenzyl)thio]-9-β-D-ribofuranosyl purine, were also active as modulators, but their activity was relatively weak and varied with the stimulus and the tissue. An order of potency for R-PIA, NECA, and 2-chloroadenosine could not be determined and 8-phenyltheophylline (10−5 M) was not an effective inhibitor of the effects of adenosine or the adenosine derivatives. This suggests that adenosine and its derivatives may modulate cells through mechanisms other than activation of conventional A1 and A2 receptors. A lack of specificity for the adenosine derivatives must also be considered.

Does endogenous adenosine have a role in the cardiac responses to isoprenaline and in the rapid fade of the inotropic response of perfused heart?

1994 ◽  
Vol 72 (2) ◽  
pp. 152-160 ◽  
Author(s):  
Kenneth J. Broadley ◽  
Andrew N. A. Wilson
Keyword(s):  
Guinea Pig ◽  
Adenosine Deaminase ◽  
Papillary Muscles ◽  
Inotropic Response ◽  
Force Of Contraction ◽  
Depressant Effect ◽  
Response Curves ◽  
Endogenous Adenosine ◽  
Left And Right ◽  
Right Atria

The role of endogenous adenosine during the β-adrenoceptor responses to isoprenaline of guinea-pig isolated cardiac preparations was examined. Insignificant effects of adenosine deaminase (0.3 U∙mL−1) on cumulative concentration–response curves for isoprenaline on isolated left and right atria and papillary muscles indicated a negligible depressant effect of endogenous adenosine during these responses. The increase in force of contraction to an infusion of isoprenaline (14 nM) in perfused spontaneously beating hearts rapidly waned while the infusion continued, whereas the increase in rate of contraction remained constant throughout the infusion. The degree of fade was less in paced preparations (5 Hz), indicating that it was only in part due to the rate increase exerting some mechanical constraint on the force of contraction. The P1-purinoceptor antagonist 8-phenyltheophylline (12 μM) and adenosine deaminase (0.3 U∙mL−1) did not enhance the peak responses to the isoprenaline infusion. The fade of the inotropic response in both spontaneous and paced hearts was also not attenuated by the presence of 8-phenyltheophylline or adenosine deaminase. The fade was not, therefore, due to release of endogenous adenosine exerting a depressant effect. Whether this declining inotropic response represents a form of rapid desensitization remains to be determined.Key words: guinea-pig perfused hearts, left and right atria, papillary muscles, β-adrenoceptor agonist, endogenous adenosine.

Fine-tuning modulation of myenteric motoneurons by endogenous adenosine: On the role of secreted adenosine deaminase

2006 ◽  
Vol 126-127 ◽  
pp. 211-224 ◽  
Author(s):  
Paulo Correia-de-Sá ◽  
Sara Adães ◽  
M. Alexandrina Timóteo ◽  
Cátia Vieira ◽  
Teresa Magalhães-Cardoso ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Fine Tuning ◽  
Endogenous Adenosine

scholarly journals Role of chloride channels in bradykinin-induced guinea pig airway vagal C-fibre activation

2005 ◽  
Vol 566 (1) ◽  
pp. 205-212 ◽  
Author(s):  
Min-Goo Lee ◽  
Donald W. MacGlashan ◽  
Bradley J. Undem
Keyword(s):  
Guinea Pig ◽  
Chloride Channels ◽  
C Fibre
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