| Abstrakt: |
The functional role of 3-adrenergic receptors in the heart is still not clear. The actions of two widely used 3-adrenoceptor agonists, such as BRL 37344 and CGP 12177, were studied in the isolated guinea pig heart, perfused at constant pressure according to the Langendorff technique. Heart contractility (dP/dt, first derivative of pressure measured over time) and coronary flow (CF) were assessed simultaneously. BRL 37344 and CGP 12177A at a concentration range of 10−8–10−5Mincreased dP/dt and CF. The selective 3-antagonist L-748337 (10−6M) did not significantly influence either BRL 37344 or CGP 12177A–induced responses. However, both dP/dt and CF responses to BRL 37344 and CGP 12177A at a concentration of 10−7Mwere abolished in the presence of the 1/2-antagonist nadolol (10−5M). In contrast, cardiovascular responses to CGP 12177A at a higher concentration of 10−5Mwere hardly inhibited by nadolol (10−5M). In addition, BRL 37344 and CGP 12177A at concentrations as low as 10−8Malmost completely abolished an isoprenaline-induced increase in contractility, suggesting that both BRL 37344 and CGP 12177A display 1-antagonistic properties. These data suggest that the stimulatory cardiovascular responses to BRL 37344 at a full range of concentrations, and CGP 12177A at a low concentration of 10−7M, are not mediated by 3-adrenergic receptors, but rather by activation of 1- or 2-adrenergic receptors. Cardiovascular effects of CGP 12177A at a high concentration of 10−5Mare independent of 1/2/3-adrenergic receptors. Summing up, it seems that in the isolated guinea pig heart the functional role of 3-adrenoceptors is not significant. Nonetheless, BRL 37344 and CGP 12177A are not ideal tools for investigation of 3-adrenergic receptor-dependent effects, because these compounds interact with other types of -adrenergic receptors. |
