INFLUENCE OF ALBUMIN ON ISOPRENALINE AND PROPRANOLOL EFFECTS ON ISOLATED RAT UTERUS

We investigated the effect of albumin (6%) on the (+/-)-isoprenaline-i nduced relaxation of strips of isolated rat uterus and its antagonism by (-)-propranolol. The mean isoprenaline EC50 in the presence of albu min was significantly less than that in the absence of albumin (geomet ric mean 1.94 +/- 3.33 versus 3.21 +/- 3.50 nM, respectively; n = 14; p = 0.006, paired t test). This indicates enhancement of isoprenaline activity by albumin which could not be explained by protein binding, a s this would have reduced activity. Geometric mean control K(B) values for inhibition of isoprenaline by propranolol at 26.8 and 500 nM were 0.835 +/- 1.68 (n = 10) and 0.889 +/- 1.60 nM (n = 34), respectively. In the presence of 6% albumin, K(B) for propranolol was increased sig nificantly to 13.3 +/- 1.8 nM (n = 27, p < 0.001). Calculation of K(B) in terms of the measured propranolol unbound concentration of 26.8 nM , after taking into account the lower isoprenaline EC50 in the presenc e of albumin, yielded a mean value of 0.725 +/- 1.86 nM, which was not significantly different from either control (p > 0.05). Therefore, pr opranolol activity was as predicted by the unbound drug concentration in contrast to isoprenaline activity. We conclude that albumin can alt er in vitro drug activity by mechanisms in addition to the reduction o f unbound drug concentration.