Differential Blockade of Guinea-pig Atrial Rate and Force Responses to (--)-noradrenaline by Practolol - an Uptake Phenomenon

The relative blockade of rate and force responses of guinea-pig isolated atria to catecholamines by practolol was compared. pA2 determinations revealed that with (--)-noradrenaline as the agonist, practolol was more effective in antagonizing rate (pA2, 6.99) than force (pA2, 6.44). This difference was absent in either atria from reserpinized animals incubated with phenoxybenzamine and tropolone or atria incubated with cocaine. Similarly, when (--)-isoprenaline was the agonist, force and rate pA2 values were identical, suggesting that rate and force beta1-adrenoceptors do not differ. The preferential blockade of (--)-noradrenaline-induced rate responses in untreated atria was attributed to the operation of a saturable neuronal uptake mechanism which differs between left and right atria. To avoid high (--)-noradrenaline concentrations encountered during pA2 determinations, the % reduction of responses to single doses of (--)-noradrenaline by practolol were measured in untreated atria. Far from confirming the lack of receptor differentiation indicated by the pA2 determinations, this study revealed force to be more practolol sensitive. The relative merits of the two methods are discussed in an attempt to resolve the question whether rate and force beta1-adrenoceptors differ.