Muscarinic stimulation of prostanoid synthesis by the isolated rat trachea: calcium dependency and effect of cortisol and cigarette smoke.
Tracheal prostanoid synthesis was stimulated by parasympathomimetics: arecoline greater than carbachol = methacholine greater than acetylcholine much greater than arecaidine. McNA343, dimethyl phenyl piperazinium (DMPP), nicotine, potassium and isoprenaline were without effect. Prostanoid synthesis was also stimulated by Ca2+ ionophore A23187 and arachidonic acid (AA). Carbachol-stimulated prostanoid synthesis was inhibited by cholinergic antagonists (atropine greater than ipratropium bromide much greater than gallamine greater than pirenzepine); adrenaline and isoprenaline were without effect. Carbachol-stimulated prostanoid synthesis was also inhibited by the Ca2+-channel blockers, nifedipine, diethylstilboestrol and TMB-8. Hydrocortisone and betamethasone inhibited carbachol- and A23187-stimulated, but not AA-stimulated, prostanoid synthesis following an 18 h tissue culture. Cigarette smoke extracts had a biphasic effect on carbachol-, A23187- and AA-stimulated prostanoid synthesis (potentiation at low concentrations, inhibition at high concentrations of extracts). These data demonstrate (1) that rat tracheal prostanoid synthesis is stimulable by activation of muscarine receptor-linked Ca2+ mobilisation, and (2) that tracheal prostanoid synthesis may be involved in secretion of mucus, the disruption of which by cigarette smoking may be related to the pathophysiology of airway disease.
Jeremy
J Y
JY
Department of Chemical Pathology and Human Metabolism, Royal Free Hospital and School of Medicine, London, U.K.
Mikhailidis
D P
DP
Dandona
P
P
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D001623:Betamethasone / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012907:Smoking / Q000378:metabolism*; D013566:Sympathomimetics / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D002121:Calcium Channel Blockers; D010276:Parasympatholytics; D011453:Prostaglandins; D011976:Receptors, Muscarinic; D013566:Sympathomimetics; D001623:Betamethasone; D000109:Acetylcholine; D002118:Calcium; D006854:Hydrocortisone