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Effects of cyclic AMP and analogues on neurogenic transmission in the rat tail artery
Author(s) -
Ouedraogo Sylvin,
Stoclet JeanClaude,
Bucher Bernard
Publication year - 1994
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.1476-5381.1994.tb14782.x
Subject(s) - forskolin , isoprenaline , adenosine , medicine , endocrinology , protein kinase a , chemistry , stimulation , cyclic nucleotide , guanosine , cyclic adenosine monophosphate , cyclase , biology , kinase , biochemistry , nucleotide , receptor , gene
1 The effects of two 8‐substituted analogues of adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) were compared with those of forskolin and isoprenaline on [ 3 H]‐noradrenaline release and vasoconstriction induced by electrical field stimulation (24 pulses at 0.4 Hz, 200 mA, 0.3 ms duration) in the rat tail artery, in the absence and in the presence of protein kinase inhibitors. 2 8‐Bromo‐adenosine 3′:5′‐cyclic monophosphate (8‐bromo‐cyclic AMP, 10–300 μ m ), 8‐(4‐chlorophenylthio)‐adenosine 3′:5′ cyclic monophosphate (8‐pCPT‐cycic AMP, 3–300 μ m ), forskolin (0.3–10 μ m ) and isoprenaline (1 n m –1 μ m ) all concentration‐dependently enhanced stimulation‐induced [ 3 H]‐noradrenaline release. The effect of cyclic AMP analogues was larger (2.5 fold at 300 μ m ) than those of cyclic AMP elevating drugs (1.6 fold at 10 μ m for forskolin and 1.5 fold at 30 n m for isoprenaline). 3 At concentrations active at the prejunctional level, the four drugs had differential effects on stimulation‐induced vasoconstriction, which was enhanced by the two cyclic AMP analogues, decreased by forskolin and not significantly altered by isoprenaline. 4 The [ 3 H]‐noradrenaline release‐enhancing effects of 8‐bromo‐cyclic AMP, forskolin and isoprenaline were significantly decreased by the cyclic AMP‐dependent protein kinase (PKA) inhibitor {N‐[2‐((3‐(4‐bromophenyl)‐2‐propenyl)‐amino)‐ethyl]‐5‐isoquinolinesulphonamide, di‐hydrochloride} (H‐89; 100 n m ). By contrast they were unaffected by the cyclic GMP‐dependent protein kinase (PKG) inhibitor, 8‐bromo‐guanosine 3′:5′‐cyclic monophosphorothioate, Rp‐isomer (Rp‐8‐bromo‐cyclic GMPS; 10 μ m ). At the same concentrations the PKA inhibitor attenuated only the nerve‐induced vasoconstrictor responses obtained in the presence of 8‐bromo‐cyclic AMP, whereas the PKG inhibitor did not modify that obtained in the presence of 8‐bromo‐cycic AMP or forskolin. 5 Exposure to the protein kinase C (PKC) activator, phorbol 12‐myristate 13‐acetate (1 μ m ) enhanced nerve‐evoked [ 3 H]‐noradrenaline release, and this effect was decreased by the PKC inhibitor, 2‐[1‐(3‐dimethylaminopropyl)‐indol‐3‐yl]‐3‐(‐indol‐3‐yl)‐maleimide (GF 109203X; 100 n m ). However, the latter drug did not modify the enhancing effect of 8‐bromo‐cyclic AMP on [ 3 H]‐noradrenaline release. 6 It is concluded that activation of cyclic AMP‐dependent protein kinase is involved in the enhancing effect of cyclic AMP‐elevating compounds on prejunctional release of noradrenaline. In addition the results provide no clear‐cut evidence for a vasodilator role of PKA.