Article date: May 1994
By: Belay Tesfamariam, Guy T. Allen, in Volume 112, Issue 1, pages 55-58
The present study was undertaken to characterize the β3‐adrenoceptor agonist activity of ICI‐215001 and to determine whether it exhibits additional activities on β1‐ and β2‐adrenoceptors in isolated spontaneously beating atrium, trachea and ileum of guinea‐pig.
In guinea‐pig atrium, isoprenaline, a non‐selective β‐adrenoceptor agonist, caused concentration‐dependent, positive chronotropic effects that were inhibited by atenolol, a selective β1‐antagonist. ICI‐215001 also competitively antagonized the increase in heart rate caused by isoprenaline.
ICI‐215001 exhibited low intrinsic activity at increasing the beating rate of atrium and no activity on resting or induced tone of tracheal strips.
In strips of guinea‐pig trachea, contracted submaximally with carbachol, isoprenaline, caused concentration‐dependent relaxations. Both ICI‐118551, a selective β2‐adrenoceptor antagonist, and ICI‐215001 competitively inhibited the relaxations caused by isoprenaline.
In isolated strips of guinea‐pig ileum longitudinal smooth muscle contracted with histamine, isoprenaline and ICI‐215001 caused relaxations which were inhibited by alprenolol, a β‐adrenoceptor antagonist with modest affinity for β3‐adrenoceptors, but were resistant to ICI‐118551 and atenolol.
These results indicate that ICI‐215001 exhibits β3‐adrenoceptor agonist activity as demonstrated by relaxations mediated via atypical β‐adrenoceptors in the longitudinal smooth muscle of guinea‐pig ileum. Further, the studies demonstrate that ICI‐215001 can act as an antagonist at β1‐ and β2‐adrenoceptors in situations where its intrinsic agonist activity is low.
The present study was undertaken to characterize the β3‐adrenoceptor agonist activity of ICI‐215001 and to determine whether it exhibits additional activities on β1‐ and β2‐adrenoceptors in isolated spontaneously beating atrium, trachea and ileum of guinea‐pig.
In guinea‐pig atrium, isoprenaline, a non‐selective β‐adrenoceptor agonist, caused concentration‐dependent, positive chronotropic effects that were inhibited by atenolol, a selective β1‐antagonist. ICI‐215001 also competitively antagonized the increase in heart rate caused by isoprenaline.
ICI‐215001 exhibited low intrinsic activity at increasing the beating rate of atrium and no activity on resting or induced tone of tracheal strips.
In strips of guinea‐pig trachea, contracted submaximally with carbachol, isoprenaline, caused concentration‐dependent relaxations. Both ICI‐118551, a selective β2‐adrenoceptor antagonist, and ICI‐215001 competitively inhibited the relaxations caused by isoprenaline.
In isolated strips of guinea‐pig ileum longitudinal smooth muscle contracted with histamine, isoprenaline and ICI‐215001 caused relaxations which were inhibited by alprenolol, a β‐adrenoceptor antagonist with modest affinity for β3‐adrenoceptors, but were resistant to ICI‐118551 and atenolol.
These results indicate that ICI‐215001 exhibits β3‐adrenoceptor agonist activity as demonstrated by relaxations mediated via atypical β‐adrenoceptors in the longitudinal smooth muscle of guinea‐pig ileum. Further, the studies demonstrate that ICI‐215001 can act as an antagonist at β1‐ and β2‐adrenoceptors in situations where its intrinsic agonist activity is low.
DOI: 10.1111/j.1476-5381.1994.tb13028.x
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