, Volume 159, Issue 1, pp 199–210 | Cite as

Dynamics of isoproterenol subsensitivity in guinea pig airway smooth muscle

Comparison of tissue cAMP levels and airway smooth muscle relaxation
  • W. R. Tipton
  • H. S. Nelson
  • J. F. Souhrada
  • H. G. Morris
  • K. W. Jacobson
Original Articles


Possible subsensitivity to the bronchodilator effects of beta adrenergic agonists has been a clinical concern for the past decade. We have examined this possibility in guinea pigs who were treated in vivo with isoproterenol, either 375 µg/kg BW (single dose) or 75 µg/kg BW every 20 min for 5 h (multiple dose). Tracheal segments were isolated from control and treated animals at 1/2, 1, 2, 4, and 6 h after the last injection and the isoproterenol cumulative dose-response relaxation curves were examined in vitro (n=92 prep.). Segments of the same tracheas were also used for measurement of “basal” cAMP and cAMP response to isoproterenol stimulation in vitro (n=78 prep.).

Subsensitivity to isoproterenol-induced tracheal relaxation was present 1 h after single or multiple doses of in vivo treatment. At all other times the ED50 for tracheal relaxation was similar to the control group. There were marked alterations in tracheal cAMP responses to adrenergic stimulation in vitro. After single doses of in vivo treatment, cAMP response was markedly enhanced at 1/2 h, suppressed at 1 h, and normal thereafter. After multiple doses, cAMP was suppressed for 6 h. This difference in the duration of subsensitivity in the two systems suggests that the beta adrenergic effects on airway smooth muscle may be mediated through mechanisms other than tissue cAMP levels.

Key words

Cyclic nucleotides Tracheal smooth muscle Beta adrenergic agonists Subsensitivity 


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Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • W. R. Tipton
    • 1
  • H. S. Nelson
    • 1
  • J. F. Souhrada
    • 2
  • H. G. Morris
    • 2
  • K. W. Jacobson
    • 3
  1. 1.Allergy-Immunology ServiceFitzsimons Army Medical CenterAurora
  2. 2.National Jewish Hospital and Research CenterDenver
  3. 3.EugeneUSA

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