TY - JOUR
T1 - Increased cholinergic antagonism underlies impaired β-adrenergic response in ovalbumin-sensitized guinea pigs
AU - Wills-Karp, M.
AU - Gilmour, M. I.
PY - 1993
Y1 - 1993
N2 - 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.
AB - 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.
KW - airway smooth muscle
KW - functional antagonism
KW - muscarinic receptors
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U2 - 10.1152/jappl.1993.74.6.2729
DO - 10.1152/jappl.1993.74.6.2729
M3 - Article
C2 - 8396106
AN - SCOPUS:0027299354
SN - 8750-7587
VL - 74
SP - 2729
EP - 2735
JO - Journal of applied physiology
JF - Journal of applied physiology
IS - 6
ER -