Parasympathetic stimulation as a mechanism for platelet-activating factor-induced contractile responses in the lung.
Platelet-activating factor (PAF) contracts isolated parenchymal tissues from guinea-pig lung at nanomolar concentrations. Previous studies indicate that, although significant quantities of thromboxane A2 are released from lung tissues stimulated with PAF, inhibition of thromboxane synthesis does not significantly diminish the in vitro spasmogenic response. In contrast, treatment of the tissues with the specific neurotoxin tetrodotoxin or with atropine results in significant inhibition of PAF-induced contractions. Contractile responses to the other lipid spasmogens leukotrienes C4 and D4 and prostaglandin F2 alpha and the stable thromboxane A2 analog U-46619 or histamine are not altered by these drugs. In the presence of physostigmine, an acetylcholinesterase inhibitor, the PAF-induced contractions of lung strips were modestly enhanced, consistent with release of endogenous acetylcholine. The rate of degradation of PAF in lung tissue was not altered by physostigmine. Lack of inhibition by the preganglionic blocking agent hexamethonium localizes the site of PAF action to a point at or distal to the parasympathetic ganglion but proximal to the neuromuscular junction. Thus PAF, or a metabolite thereof, acts presynaptically on cholinergic neurons in lung tissues to effect smooth muscle contraction, and this phospholipid may constitute a link between the immunologic humoral and autonomic pathways that lead to bronchoconstriction.
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D010276:Parasympatholytics; D010972:Platelet Activating Factor; D013779:Tetrodotoxin; D001285:Atropine; D000109:Acetylcholine; D007213:Indomethacin