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Inhibition of histamine‐stimulated inositol phospholipid hydrolysis by agents which increase cyclic AMP levels in bovine tracheal smooth muscle
Author(s) -
Hall I.P.,
Donaldsona J.,
Hill S.J.
Publication year - 1989
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.1476-5381.1989.tb11992.x
Subject(s) - ibmx , histamine , rolipram , forskolin , inositol phosphate , medicine , chemistry , endocrinology , inositol , phosphodiesterase , ionomycin , phospholipid , phosphodiesterase inhibitor , phosphate , biochemistry , biology , enzyme , in vitro , receptor , membrane
1 The effect on histamine‐stimulated [ 3 H]‐inositol phosphate accumulation of a range of agents which increase the accumulation, or mimic the actions, of cyclic AMP has been investigated in bovine tracheal smooth muscle. 2 Salbutamol (1 μ m ), forskolin (1 μ m ) and vasoactive intestinal peptide (VIP, 1 μ m ) inhibited the inositol phosphate response to 0.1 m m histamine and increased the accumulation of [ 3 H]‐cyclic AMP in [ 3 H]‐adenine‐labelled slices of bovine tracheal smooth muscle. The effect on inositol phospholipid hydrolysis was mimicked by the membrane permeant analogues of cyclic AMP, dibutryl‐cyclic AMP (1 m m ) and 8‐bromo‐cyclic AMP (1 m m ). 3 In contrast to salbutamol, which was equally effective at producing the two effects, forskolin produced large increases in [ 3 H]‐cyclic AMP accumulation (EC 50 = 1.2 μ m ) at much higher concentrations than those required for inhibition of histamine‐stimulated [ 3 H]‐inositol phosphate accumulation (EC 50 = 0.09 μ m ). However, significant increases in [ 3 H]‐cyclic AMP accumulation, of similar magnitude to those obtained with salbutamol and VIP, were observed over the concentration range appropriate for inhibition of the inositol phosphate response to histamine. 4 In the presence of histamine (0.1 m m ), isobutylmethylxanthine (IBMX, 1 m m ) and rolipram (0.1 m m ) both significantly ( P < 0.05) elevated tissue [ 3 H]‐cyclic AMP levels. IBMX, rolipram and (to a lesser extent) SKF 94120 significantly ( P < 0.05) reduced histamine‐stimulated [ 3 H]‐inositol phosphate accumulation by 81%, 68% and 20%, respectively. M&B 22948 was without a significant effect on either [ 3 H]‐cyclic AMP or histamine‐induced [ 3 H]‐inositol phosphate accumulation. 5 Both rolipram and forskolin reduced the increase in incorporation of [ 3 H]‐inositol into membrane phospholipids which followed stimulation with histamine. However, a significant inhibition of [ 3 H]‐inositol phosphate accumulation could be demonstrated under conditions in which there was no change in the level of [ 3 H]‐inositol incorporation.