The influence of animal age on beta-adrenoceptor density and function in tracheal airway smooth muscle.
We examined the influence of animal age on the functional response of guinea-pig (0-156 weeks) and rat (4-136 weeks) isolated tracheal tissue to beta-adrenoceptor agonists. In addition, the binding density and affinity of [125I]iodocyanopindolol ([125I]CYP) binding to tracheal tissue was examined with respect to animal age. Significant age-related changes in isoprenaline potency were observed in tracheal ring preparations taken from animals during the early maturation phase of animal growth in the guinea-pig and rat. In addition, in rat isolated tracheal tissue, age-related decreases in fenoterol potency were observed during senescence, but not maturation. The changes in the functional responsiveness of tracheal tissue were not reflected by changes in the binding density or affinity for [125I]cyanopindolol ([125I]CYP) of beta-adrenoceptors, or in changes in specific autoradiographic grain density over smooth muscle tissue. In both guinea-pig and rat, no significant age-related changes in the influence of catechol-O-methyl transferase (COMT) or of extraneuronal uptake inhibition were detected. This study has demonstrated significant age-related changes in the responsiveness of guinea-pig and rat isolated tracheal tissue to beta-adrenoceptor agonists that were not related to changes in the density or affinity of the beta-adrenoceptor population or in the activity of COMT or extraneuronal uptake. The possibility of age-related changes in receptor-signal transduction coupling should be explored.
Preuss
J M
JM
Department of Pharmacology, University of Western Australia, Nedlands, Perth. janetp@ichr.uwa.edu.au
Rigby
P J
PJ
Goldie
R G
RG
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001345:Autoradiography; D002394:Catechol O-Methyltransferase / Q000502:physiology; D006224:Cricetinae; D005280:Fenoterol / Q000494:pharmacology; D066298:In Vitro Techniques; D020120:Iodocyanopindolol / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012044:Regression Analysis; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D005280:Fenoterol; D020120:Iodocyanopindolol; D002394:Catechol O-Methyltransferase; D007545:Isoproterenol