β ‐Adrenoceptor stimulation inhibits histamine‐stimulated inositol phospholipid hydrolysis in bovine tracheal smooth muscle

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Abstract
1 Histamine and carbachol produced concentration-related increases in the accumulation of 3Hinositol phosphates in slices of bovine tracheal smooth muscle. 2 Noradrenaline alone produced a small stimulation of 3H-inositol phosphate accumulation which was inhibited by the α-adrenoceptor antagonist phentolamine. In contrast, when noradrenaline (0.1 mm) was added simultaneously with histamine it significantly reduced the inositol phosphate response to high (≥0.1mm) concentrations of histamine. However, noradrenaline had no inhibitory effect on the carbachol-induced inositol phosphate response. 3 The non-selective β-agonist isoprenaline (IC50 = 0.08 μm) and the β2-selective agonist salbutamol (IC50 = 0.29 μm) both produced a dose-related inhibition of the inositol phosphate response to 0.1 mM histamine. The inhibitory effect of salbutamol was antagonized by propranolol (KA = 2.4 × 109M−1) and the β2-selective adrenoceptor antagonist ICI 118551 (KA = 1.7 × 109 M−1). 4 The accumulation of 3H-inositol phosphates induced by histamine increased steadily over a 40 min period after an initial lag period of 3–4 min. Following the simultaneous addition of histamine and salbutamol there was a further delay of 3–4 min before the appearance of the inhibitory effect of salbutamol. 5 The effect of histamine on inositol phosphate accumulation was accompanied by a stimulation of [3H]-inositol incorporation into membrane phospholipids which was reduced by the presence of salbutamol. However, when histamine was used to stimulate maximally [3H]-inositol incorporation during the prelabelling period, salbutamol produced a marked inhibition of histamine-stimulated 3H-inositol phosphate accumulation under conditions in which there was no change in the level of incorporation.

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