Increased cholinergic antagonism underlies impaired β-adrenergic response in ovalbumin-sensitized guinea pigs

M. Wills-Karp, M. I. Gilmour

Research output: Contribution to journalArticle

Abstract

The goal of this study was to determine if the hyporesponsiveness to β- adrenoceptor stimulation observed in ovalbumin-sensitized tracheal smooth muscle is due to increased cholinergic muscarinic tone or to a defect in the β-adrenergic cascade itself. We examined the effects of ovalbumin- sensitization on the responsiveness of guinea pig tracheae to agents that mediate relaxation at various steps in the β-adrenergic cascade when the tracheal tissue was preconstricted with either carbachol or histamine. Ovalbumin sensitization caused significant reductions in the maximal relaxations both to the β-adrenergic agonist isoproterenol and to prostaglandin E2 (PGE2) in guinea pig trachealis when the tracheal tissue was preconstricted with the muscarinic agonist carbachol. In contrast, sensitization had no effect on the ability of PGE2 and isoproterenol to relax histamine contractions. Preconstricting the tissues with increasing concentrations of KCl reduced the effectiveness of isoproterenol to relax equally airway tissues from both sensitized and control animals. Forskolin- induced relaxations of trachealis muscle were not altered with sensitization. When tracheal tissues were precontracted with increasing concentrations of carbachol, the effectiveness of isoproterenol and PGE2 to relax airway tissues decreased. Functional antagonism of relaxations by muscarinic agonists was enhanced in the sensitized tissues, since the concentration of carbachol necessary to reduce β-adrenoceptor-induced relaxations to the same degree as in the control animals was a log dose lower. These results suggest that the impaired β-adrenoceptor response in sensitized tissues is not due to an intrinsic defect in the β-adrenergic cascade but to an enhancement of a muscarinic cholinergic pathway.

Original languageEnglish (US)
Pages (from-to)2729-2735
Number of pages7
JournalJournal of applied physiology
Volume74
Issue number6
DOIs
StatePublished - 1993

Keywords

  • airway smooth muscle
  • functional antagonism
  • muscarinic receptors

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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