title: Influence of epithelium on beta-adrenoceptor desensitization of guinea pig tracheal smooth muscle.
abstract: The effect of tissue incubation with a beta2-agonist of denuded and intact epithelium trachea on the responsiveness to isoprenaline and beta-receptor blocked by propranolol (CR-1) was examined in this study. We examined the effect of epithelium removal on the beta-adrenoceptor desensitization resulting from incubation of guinea pig trachea in the beta-adrenergic agonist isoprenaline (10 microM). Desensitization was measured as the change in EC50, the concentration of beta-agonist that produced 50% relaxation of tracheal rings contracted with methacholine. As a second measure of desensitization, we measured the shift in EC50 resulting from incubation of tracheal rings with the beta-adrenoceptor antagonist propranolol (20 nM), expressed as CR-1 ([post-propranolol EC50/baseline EC50]-1). Initially, we measured desensitization immediately after incubation in isoprenaline; subsequently, we repeated the protocol and allowed a 30 min rest between the end of incubation and the measurement. The sensitivity of denuded epithelium trachea to isoprenaline and (CR-1) was significantly higher than that of intact epithelium only in non-incubated preparations (p<0.05 to p<0.001). Incubation to isoprenaline caused a significant reduction in the tracheal response to isoprenaline in both the denuded groups (p<0.005 for both cases) and intact epithelium groups (p<0.05 for both cases). Incubation to isoprenaline also caused a significant reduction in (CR-1) value in both the denuded groups (p<0.005 for group 2 and p<0.001 for group 4) and intact epithelium only in group 1 (p<0.05). However, the changes in EC50 due to tissue incubation with isoprenaline were significantly greater in denuded than intact epithelium trachea (p<0.05 for all cases) and for CR-1 value only in groups 1 and 2 (p<0.05). These results indicate decrease in both tracheal response to beta-agonist (tolerance) and CR-1 (due to incubation of tissues with isoprenaline), which were greater in denuded epithelium groups.
authors.affiliation: Department of Physiology, Ghaem Medical Centre, Mashhad University of Medical Sciences, Mashhad, Post Code 91735, Iran. mhboskabady@hotmail.com
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Boskabady
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Aslani
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004848:Epithelium / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000008:administration & dosage; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D011433:Propranolol / Q000008:administration & dosage; D011897:Random Allocation; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D007545:Isoproterenol