Prejunctional inhibition of cholinergic responses by prostaglandin E2 in human bronchi.
The effect of prostaglandin E2 (PGE2) on cholinergic responses elicited by electrical field stimulation (EFS) (8 Hz, 1 ms, 8 V for 10 s every 100 s) of human isolated human bronchi was studied. Indomethacin (1 microM) was found to produce approximately a 100% increase in the cholinergic response. In the presence of indomethacin, PGE2 (1-300 nM) was found to concentration-dependently inhibit the cholinergic responses to EFS. A maximal inhibition was obtained with 100 nM PGE2 which produced an 80% inhibition of the cholinergic response. By contrast 100 nM PGE2 was without significant effect on the concentration response curve to exogenously added acetylcholine. The inhibitory effect of PGE2 on the EFS-induced cholinergic responses was not modified by the large conductance Ca(2+)-activated K+ channel inhibitor charybdotoxin (100 nM). These results suggest that endogenously released prostaglandins, presumably PGE2, act to inhibit cholinergic responses by a prejunctional mechanism in human isolated bronchi. In contrast to other autocoids, this inhibition does not involve the activation of large-conductance Ca(2+)-activated K+ channels.
Ellis
J L
JL
Division of Clinical Immunology, John Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224-6801, USA.
Conanan
N D
ND
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001285:Atropine / Q000494:pharmacology; D017609:Barium Compounds / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D018999:Charybdotoxin / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D017609:Barium Compounds; D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D018727:Muscarinic Antagonists; D010455:Peptides; D026902:Potassium Channel Blockers; C024986:barium chloride; D018999:Charybdotoxin; C064719:iberiotoxin; D001285:Atropine; D015232:Dinoprostone; D000109:Acetylcholine; D007213:Indomethacin