Ca2+ influx insensitive to organic Ca2+ entry blockers contributes to noradrenaline-induced contractions of the isolated guinea pig aorta.

We determined the contribution of intracellular Ca2+ to the noradrenaline (NA, 3 X 10(-5) mmol/l)-induced contraction of the isolated guinea pig aorta. Since only about 55% of the NA-induced contraction could be attributed to intracellular Ca2+ release, we assumed that a Ca2+ influx component contributes to the NA-induced contraction. This influx component proved resistant to the organic calcium entry blockers (CEBs) nifedipine, diltiazem, flunarizine and gallopamil which, in contrast, antagonized K(+)-induced Ca2+ influx completely. Conversely, the NA-induced Ca2+ influx component could be antagonized by the inorganic cations La3+, Cd2+, Mn2+, Ni2+ and Co2+. 45Ca2+ uptake experiments also revealed that both KCl and NA induce Ca2+ influx of which only the latter one is resistant to nifedipine. It was concluded that in the guinea pig aorta NA activates a receptor-operated channel through which Ca2+ can be translocated from the extracellular space to the cytosol to contribute directly to contraction.