Effect of a 7-day treatment with idazoxan and its 2-methoxy derivative RX 821002 correction of RX 821001 on alpha 2-adrenoceptors and non-adrenoceptor idazoxan binding sites in rabbits.

摘要

1. The present study investigates the influence of a 7-day treatment with 2 mg kg-1, s.c., twice daily of RX 821002 (an alpha 2-adrenoceptor antagonist which binds only to alpha 2-adrenoceptors) or idazoxan (alpha 2-antagonist which binds to alpha 2-adrenoceptors and also to non-adrenoceptor idazoxan binding sites: NAIBS) on alpha 2-adrenoceptor (labelled with [3H]-RX 821002) and NAIBS (labelled with [3H]-idazoxan) number in three tissues (adipocytes, colocytes and platelets) in the rabbit. 2. Acute administration of RX 821002 or idazoxan increased plasma non-esterified fatty acids (NEFA) and catecholamine levels with no change in plasma glucose levels. 3. The 7-day treatment with RX 821002 or idazoxan failed to influence food intake, total body weight or perirenal adipose tissue weight. 4. RX 821002 and idazoxan increased the number of [3H]-RX 821002 binding sites in adipose tissue with no change in colocytes or platelets. 5. RX 821002 and idazoxan failed to modify [3H]-idazoxan binding sites on adipocytes and colocytes. No significant [3H]-idazoxan binding was detected on rabbit platelets. 6. The results show that a 7-day treatment with alpha 2-antagonists induces an up-regulation in adipocyte alpha 2-adrenoceptors. In contrast, this phenomenon does not involve all the tissues since colocytes and platelets escape the effects of alpha 2-antagonists. The data suggest a differential regulation of alpha 2-adrenoceptors according to their location. 7. The fact that NAIBS did not vary suggests that alpha 2-adrenoceptors and NAIBS are two different entities.(ABSTRACT TRUNCATED AT 250 WORDS)