Mechanisms underlying the inhibitory effect of Propofol on the contraction of canine airway smooth muscle

• Published in: Anesthesiology (Philadelphia) 1999-09, Vol.91 (3), p.750-759
• Main Authors: LIN, C.-C, SHYR, M.-H, TAN, P. P. C, CHIEN, C.-S, PAN, S.-L, WANG, C.-C, CHIU, C.-T, YANG, C.-M
• Format: Article
• Language: English
• Subjects: Anesthetics, Intravenous - pharmacology; Anesthetics. Neuromuscular blocking agents; Animals; Biological and medical sciences; Calcium - metabolism; Carbachol - pharmacology; Dogs; Female; In Vitro Techniques; Inositol 1,4,5-Trisphosphate - biosynthesis; Male; Medical sciences; Muscle Contraction - drug effects; N-Methylscopolamine - metabolism; Neuropharmacology; Pharmacology. Drug treatments; Propofol - pharmacology; Trachea - drug effects; Trachea - physiology
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-199909000-00028

Propofol has been shown to produce relaxation of preconstricted airway smooth muscle. Although the inhibition of calcium mobilization is supposed to be the major mechanism of action, the whole picture of the mechanisms is not completely clear. Contractile response was performed using canine tracheal rings. The effects of propofol on carbachol-induced mobilization of intracellular Ca2+ and phosphoinositide hydrolysis were measured using cultured canine tracheal smooth muscle cells by monitoring fura-2 signal and assessing the accumulation of [3H]-inositol phosphates. To detect the effect of propofol on muscarinic receptor density and affinity, [3H]N-methyl-scopolamine was used as a radioligand for receptor binding assay. Pretreatment with propofol shifts the concentration-response curves of carbachol-induced smooth muscle contraction to the right in a concentration-dependent manner without changing the maximal response. Propofol not only decreased the release of Ca2+ from internal stores but also inhibited the calcium influx induced by carbachol. In addition, carbachol-induced inositol phosphate accumulation was attenuated by propofol; the inhibitory pattern was similar to the contractile response. Moreover, propofol did not alter the density of muscarinic receptors. The dissociation constant value was not altered by pretreatment with 100 microM propofol but was significantly increased by 300 microM (propofol, 952+/-229 pM; control, 588+/-98 pM; P