Beta-adrenoceptor induced inhibition of muscarinic receptor-stimulated phosphoinositide metabolism is agonist specific in bovine tracheal smooth muscle

Abstract

The ability of the beta-adrenoceptor agonist isoprenaline to inhibit agonist-stimulated phosphoinositide metabolism was examined in bovine tracheal smooth muscle slices prelabelled with [3H]inositol. Accumulation of [3H]inositol phosphates was enhanced by the muscarinic agonists carbachol, oxotremorine and pilocarpine although the latter were only partial agonists for this response. Histamine stimulation of [3H]inositol phosphates was sensitive to mepyramine but maximal responses were only comparable to those of pilocarpine. Preincubation of tracheal slices with isoprenaline reduced the maximal phosphoinositide response to histamine and pilocarpine but the responses to carbachol and oxotremorine were unaffected. The inhibitory effect of isoprenaline (IC50 = 0.04 microM) was reversed competitively by 1 microM propranolol. The non-selective phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) (1 mM) resulted in a more severe suppression of the histamine and pilocarpine responses and also produced a significant suppression of the maximal response to oxotremorine and a small shift in the carbachol dose-response curve. The different susceptibility of agonist-stimulated phosphoinositide hydrolysis to isoprenaline and IBMX are discussed in relation to the relative intrinsic activity of the agonists and/or the role of different muscarinic receptor subtypes.