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Adenosine A 1 ‐receptor stimulation of inositol phospholipid hydrolysis and calcium mobilisation in DDT 1 MF‐2 cells
Author(s) -
White Teresa E.,
Dickenson John M.,
Alexander Stephen P.H.,
Hill Stephen J.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14317.x
Subject(s) - inositol , adenosine , inositol phosphate , chemistry , calcium , medicine , endocrinology , adenosine receptor , ryanodine receptor , agonist , receptor , biochemistry , biology
1 . The effect of adenosine receptor‐stimulation on inositol phospholipid hydrolysis and calcium mobilization has been investigated in the hamster vas deferens smooth muscle cell line DDT 1 MF‐2. 2 . Adenosine receptor stimulation increased the accumulation of total [ 3 H]‐inositol phosphates in DDT 1 MF‐2 cells prelabelled with [ 3 H]‐ myo ‐inositol. The rank order of agonist potencies was N 6 ‐cyclo‐pentyladenosine > 5′‐N‐ethylcarboxamidoadenosine > 2‐chloroadenosine > adenosine. 3 . The response to 2‐chloroadenosine was antagonized by the antagonists 8‐cyclopentyl‐1,3‐dipropylxanthine ( K D 1.2 n m ), PD 115,199 ( K D 39 n m ) and 8‐phenyltheophylline ( K D 31 n m ). 4 . The inositol phosphate response to 2‐chloradenosine (10 μ m ) was not significantly altered when the extracellular Ca 2+ ion concentration was reduced from 2.4 m m to 1.2 m m or 0.6 m m . Under calcium‐free conditions, however, a reduced but still significant response to 2‐chloroadenosine was evident (39 ± 10% of the response in calcium‐containing medium). 5 . The 5‐lipoxygenase inhibitor AA861 (10 and 100 μ m ) inhibited the inositol phosphate response to 2‐chloroadenosine by 40 ± 9% and 60 ± 4% respectively. The cyclo‐oxygenase inhibitor, indomethacin, however, was without significant effect at 1 μ m . 6 . 2‐Chloroadenosine stimulated an increase in intracellular free Ca 2+ ion concentration in fura‐2 loaded DDT 1 MF‐2 cells in calcium‐free medium containing 0.1 m m EGTA, which could be inhibited by the adenosine A 1 ‐receptor antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (0.1 μ m ). 7 . These data suggest that adenosine A 1 ‐receptor stimulation results in inositol phospholipid hydrolysis and calcium mobilization from intracellular stores in DDT 1 MF‐2 cells.