Agonist-induced inositol phosphate responses in bovine airway submucosal glands

Agonist-induced inositol phosphate responses were investigated in bovine airway submucosal glands prelabeled with [3H]inositol. The agents used included muscarinic, adrenergic, and histaminergic agonists and NaF as a direct stimulant of phosphoinositidase C. Carbachol (1 microM-1 mM) produced concentration-related [3H]-inositol phosphate formation [maximal response 7.3-fold, half-maximal effective concentration (EC50) 47 microM]. This response was inhibited by atropine [affinity constant (Ka) 1.5 x 10(9) M-1], suggesting the involvement of a muscarinic receptor. Histamine (EC50 66 microM, 2.4-fold stimulation) and norepinephrine (EC50 28 microM, 2.7-fold stimulation) also produced concentration-dependent [3H]inositol phosphate responses. The response to histamine was inhibited by mepyramine (Ka 1.9 x 10(8) M-1), and the response to norepinephrine was inhibited by phentolamine (Ka 1.3 x 10(8) M-1) and prazosin (Ka 2.3 x 10(8) M-1), indicating the involvement of H1 and alpha 1-receptors, respectively, in these responses. NaF also produced concentration-dependent [3H]inositol phosphate formation compatible with the involvement of a G protein in this response. These results demonstrate that a range of secretagogues induce inositol phosphate responses in bovine airway submucosal glands. This response may underlie stimulus response coupling in this tissue.