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Pharmacologic differentiation between pre- and postjunctional alpha 2-adrenoceptors by SK&F 104078
R R Ruffolo1, A C Sulpizio, A J Nichols
1Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, PA 19406-0939.
Naunyn-Schmiedeberg'S Archives of Pharmacology
|October 1, 1987
Summary
SK&F 104078 selectively blocks postjunctional alpha 2-adrenoceptors without affecting prejunctional alpha 2-adrenoceptors. This suggests distinct subtypes of alpha 2-adrenoceptors, challenging the notion of a homogeneous receptor population.
Area of Science:
- Pharmacology
- Adrenergic Receptor Research
Background:
- Most alpha 2-adrenoceptor antagonists lack selectivity between pre- and postjunctional receptors.
- This has led to the assumption of a single, homogeneous population of alpha 2-adrenoceptors.
Purpose of the Study:
- To investigate the selectivity of SK&F 104078 for pre- versus postjunctional alpha 2-adrenoceptors.
- To determine if alpha 2-adrenoceptors represent distinct subtypes.
Main Methods:
- In vitro studies using canine and rabbit saphenous veins, canine saphenous artery, and human platelets.
- In vivo studies in pithed rats.
- Assessment of antagonist activity at pre- and postjunctional alpha 2-adrenoceptors.
Main Results:
- SK&F 104078 acted as a potent, competitive postjunctional alpha 2-adrenoceptor antagonist (Kd ≈ 100 nmol/l) in various tissues.
- SK&F 104078 was inactive at prejunctional alpha 2-adrenoceptors in atria and guinea-pig ileum up to 10,000 nmol/l.
- SK&F 104078 selectively blocked postjunctional arterial alpha 2-adrenoceptors in vivo in pithed rats.
Conclusions:
- Pre- and postjunctional alpha 2-adrenoceptors are likely discrete subtypes.
- SK&F 104078 is a valuable tool for differentiating these alpha 2-adrenoceptor subtypes.