Influence of epithelium on beta-adrenoceptor desensitization of guinea pig tracheal smooth muscle.
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.
Boskabady
Mohammad Hossein
MH
Department of Physiology, Ghaem Medical Centre, Mashhad University of Medical Sciences, Mashhad, Post Code 91735, Iran. mhboskabady@hotmail.com
Aslani
Mohammad Reza
MR
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*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D007545:Isoproterenol