Platelet aggregation increases cholinergic neurotransmission in canine airway

To determine whether thromboxane A₂ released from aggregating platelets increases the contractile response of airway smooth muscle to cholinergic nerve stimulation and, if so, what the mechanism of action is, we studied in vitro bronchial segments from dogs under isometric conditions. The contractile responses to electrical field stimulation at 30 s and 1 min after the addition of autologous platelets were increased by 11.1 ± 3.2 (SD) and 20.7 ± 5.4%, respectively, and were increased by 11.1 ± 3.2 (SD) and 20.7 ± 5.4%, respectively, and were accompanied by the release of thromboxane A₂. These effects were inhibited either by pretreatment of platelets with indomethacin or by addition of the thromboxane A₂ receptor antagonist SQ 29548. Likewise, the thromboxane A₂ mimetic U 46619, in subthreshold doses (i.e., insufficient to increase base-line tension), increased electrical field stimulation-induced contraction by 18.7 ± 4.8%. The increase was greater in the presence of a concentration of physostigmine that did not cause spontaneous contraction and was blocked by SQ 29548 but not by hexamethonium or by phentolamine. Methacholine-induced contractions were unaffected by U 46619. These results indicate that aggregating platelets, by releasing thromboxane A₂, increase the airway contractile response to neural stimulation probably by the accelerated release of acetylcholine.