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Does treatment with beta-adrenoceptor antagonists in vivo alter human adenylate cyclase responsiveness in vitro?
M C Michel1, M Klüppel, T Philipp
1Department of Medicine, University of Essen, Germany.
Abstract:
1. Treatment with beta-adrenoceptor antagonists in vivo can alter adenylate cyclase responsiveness in the human heart. We have determined the effects of treatment with four different beta-adrenoceptor antagonists in vivo on the responsiveness of lymphocyte and platelet adenylate cyclase in vitro in healthy volunteers. 2. Propranolol (non-selective, 4 x 40 mg day), bisoprolol (beta 1-selective, 1 x 10 mg day), and ICI 118.551 (beta 2-selective, 3 x 25 mg day) were tested as drugs without and pindolol (non-selective, 2 x 5 mg day) as a drug with intrinsic sympathomimetic activity. Adenylate cyclase stimulation by GTP, prostaglandin E1 and forskolin was determined before, after a 7 day treatment period and 7 days after drug withdrawal. 3. Neither treatment with or withdrawal of any of the beta-adrenoceptor antagonists altered adenylate cyclase responsiveness. 4. We conclude that adenylate cyclase responsiveness in circulating blood cells underlies different regulatory mechanisms than that in solid tissues such as the human heart. Our data suggest that circulating blood cells do not always reflect alterations in solid tissues.
Insights
Beta-adrenoceptor antagonists did not alter adenylate cyclase responsiveness in blood cells. This suggests that circulating blood cells may not always reflect changes occurring in solid tissues like the human heart.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Cellular Biology
Background:
- Beta-adrenoceptor antagonists are used to treat various cardiovascular conditions.
- These drugs are known to affect adenylate cyclase activity in cardiac tissue.
- It remains unclear if these effects are mirrored in circulating blood cells.
Purpose of the Study:
- To investigate the in vivo effects of beta-adrenoceptor antagonists on adenylate cyclase responsiveness in human lymphocytes and platelets.
- To compare the responsiveness of blood cell adenylate cyclase to that of cardiac tissue.
Main Methods:
- Healthy volunteers were treated with four different beta-adrenoceptor antagonists (propranolol, bisoprolol, ICI 118.551, pindolol) for 7 days.
- Adenylate cyclase responsiveness was measured in vitro using stimulants like GTP, prostaglandin E1, and forskolin.
- Measurements were taken before treatment, after 7 days of treatment, and 7 days after drug withdrawal.
Main Results:
- Treatment with any of the tested beta-adrenoceptor antagonists did not alter adenylate cyclase responsiveness in lymphocytes or platelets.
- Withdrawal of the drugs also showed no significant effect on adenylate cyclase responsiveness.
- These findings indicate a lack of correlation between blood cell and solid tissue responses.
Conclusions:
- Adenylate cyclase responsiveness in circulating blood cells differs from that in solid tissues such as the human heart.
- Circulating blood cells may not serve as reliable indicators for alterations in solid tissue responses to beta-adrenoceptor antagonists.