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Muscarinic receptor interaction with full and partial beta-adrenoceptor agonists in the rat colon strip
B Ek1
1Department of Pharmacology and Biochemistry, Hässle Cardiovascular Research Laboratories, Mölndal, Sweden.
Abstract:
beta-Adrenoceptor agonists inhibit contractile activity in isolated colon strips. In order to demonstrate that beta-adrenoceptors are located at different functional levels within the colon wall, increasing concentrations of muscarinic agonists were used to interact functionally with the beta-adrenoceptor-mediated inhibition of spontaneous colon activity. The effects of the full agonists isoprenaline and terbutaline and of the partial agonist prenalterol were functionally antagonized by carbachol (0.03 and 0.3 mumol/l) and bethanechol (1.3 and 30 mumol/l). This functional antagonism was parallelled by an increase in baseline tension and spontaneous contractile activity of the isolated colon strip. At lower concentrations of carbachol (0.003 and 0.01 mumol/l) or bethanechol (0.03 and 0.3 mumol/l) no effect on the contractile status of the smooth muscle or on the pD2-values of the full agonists was seen. However, at these lower concentrations of muscarinic agonists a marked decrease in the maximal inhibitory response to the partial beta-adrenoceptor agonist prenalterol was demonstrated. The inhibitory response to prenalterol showed a biphasic concentration-response curve. The muscarinic antagonist atropine produced an increase in the maximal response of the high potency component of the concentration-response curve for prenalterol and an increase in the sensitivity to isoprenaline. These results demonstrate the presence of a high cholinergic tone in the colon preparation of a magnitude that clearly reduces the sensitivity to beta-adrenoceptor agonists. The different responses to full and partial beta-adrenoceptor agonists in the presence of increasing concentrations of muscarinic agonists may indicate that beta-adrenoceptors are located on two different functional units within the colon wall.
Insights
Beta-adrenoceptors in the colon wall are modulated by cholinergic tone. Muscarinic agonists reveal distinct functional levels of beta-adrenoceptors, impacting colon smooth muscle activity.
Area of Science:
- Pharmacology
- Gastroenterology
- Smooth Muscle Physiology
Background:
- Beta-adrenoceptor agonists are known to inhibit colon contractile activity.
- Understanding the precise location and function of beta-adrenoceptors within the colon wall is crucial for elucidating gastrointestinal motility regulation.
Purpose of the Study:
- To investigate the functional localization of beta-adrenoceptors within the colon wall.
- To explore the interaction between cholinergic tone and beta-adrenoceptor-mediated effects on colon smooth muscle.
Main Methods:
- Isolated colon strips were used to assess contractile activity.
- Increasing concentrations of muscarinic agonists (carbachol, bethanechol) were applied to study their functional interaction with beta-adrenoceptor agonists (isoprenaline, terbutaline, prenalterol).
- Concentration-response curves and maximal inhibitory responses were analyzed, with and without muscarinic antagonists (atropine).
Main Results:
- Functional antagonism of beta-adrenoceptor agonists by muscarinic agonists was observed, accompanied by increased baseline tension and spontaneous activity.
- A decrease in the maximal inhibitory response to the partial agonist prenalterol was noted at lower muscarinic agonist concentrations, suggesting a biphasic response.
- Atropine increased the maximal response of prenalterol and sensitivity to isoprenaline, indicating a significant cholinergic tone.
Conclusions:
- A high cholinergic tone exists in the colon, significantly reducing sensitivity to beta-adrenoceptor agonists.
- Differential responses to full and partial beta-adrenoceptor agonists under varying muscarinic stimulation suggest beta-adrenoceptors may reside on distinct functional units within the colon wall.