Cooling-induced supersensitivity to acetylcholine in the isolated airway smooth muscle of the rat.
Isolated tracheal and bronchial strip-chain preparations of the rat were used to study the effect of temperature on electrically or acetylcholine-induced contraction. The preparations were suspended in the organ bath containing Krebs bicarbonate solution for isometric tension recording. A decrease of bath temperature from 37 degrees C to 20 degrees C (cooling) had no effect on basal tone but augmented the contractile responses of the trachea and bronchus caused by stimulation of intramural cholinergic nerves (0.5-5 Hz) or acetylcholine (3 mumol/l-0.3 mmol/l). Cooling-induced augmentation of the contractile response to acetylcholine was not affected by pretreatment of the tissue with physostigmine (0.1 mumol/l) or tetrodotoxin (0.3 mumol/l). The affinity of acetylcholine for the tracheal muscarinic receptors at 20 degrees C, determined from its dissociation constant (KA), was not significantly different from that at 37 degrees C. On the other hand, acetylcholine-induced contraction of trachea which was incubated with isosmotic K+- rich Krebs solution and with Ca-free, EGTA (0.1 mmol/l) containing Krebs solution were both augmented at 20 degrees C. Caffeine or vanadate, each at a lower concentration than the threshold for causing contraction by itself, augmented the contractile responses of the trachea to acetylcholine (1 mumol/l-0.3 mmol/l). These potentiating effects of caffeine and vanadate were greater at 20 degrees C then 37 degrees C. From these observations, it is concluded that increased responsiveness of the rat airway smooth muscle to acetylcholine with lowered temperature may involve the acceleration of Ca release from intracellular storage sites, inhibition of Ca extrusion from the cell and or the inhibition of Ca reuptake by intracellular storage sites.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D003080:Cold Temperature; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014132:Trachea / Q000187:drug effects; D014638:Vanadates; D014639:Vanadium / Q000494:pharmacology
D009467:Neuromuscular Depolarizing Agents; D014639:Vanadium; D002110:Caffeine; D014638:Vanadates; D010042:Ouabain; D011189:Potassium Chloride; D000109:Acetylcholine; D002118:Calcium