1. The effect of intravenous infusion of catecholamines and related drugs on human platelet α 2 -adrenoceptor number and function was investgated. 2. Short (60–120 min) infusions of catecholamines with α 2 agonist activity in vivo produced attenuation of the platelet responses to adrenaline in vitro. This desensitization was specific for the adrenaline induced aggregatory response. 3. The maximum number of [ 3 H]yohimbine binding sites on platelets was not altered by adrenaline infusion. 4. The ability of adrenaline to reduce platelet cyclic AMP levels was significantly reduced after the infusions. 5. Acute infusions of α 2 -adrenoceptor agonists may alter the coupling of the platelet α 2 -adrenoceptor to adenylate cyclase.

1. α 2 -Adrenoceptors on blood platelets have been widely used as a model for α-adrenoceptors in less accessible tissues. 2. The effect of oestrogen (200 μg/day intramuscularly) on α 2 -adrenoceptor number and function was studied in immature female rabbits. α 2 -Adrenoceptor number was measured in whole platelets, and membrane preparations of forebrain, hindbrain, spleen and kidney by radioligand binding. α 2 -Adrenoceptor function was examined by measuring platelet aggregation in vitro and circulatory responses to selective α 2 -adrenoceptor agonists in vivo. 3. Oestrogen treatment resulted in a significant decrease in platelet α 2 -adrenoceptor number and function. However, no changes were observed either in receptor number in other tissues or in responses to α 2 -agonists in vivo. 4. The results suggest that oestrogen modulation of rabbit platelet α 2 -adrenoreceptor number and function may be different from that of brain, kidney and spleen. Caution should be exercised in extrapolating results from platelets to α-adrenoceptors at other sites.

1. Agonist regulation of platelet α 2 -adrenoceptors was examined in human volunteers after acute elevations of adrenoceptor agonist and during chronic elevation of plasma catecholamines in two patients with phaeochromocytoma. 2. Platelet α 2 -adrenoceptor number was measured by radioligand binding ([ 3 H]yohimbine) and α 2 -adrenoceptor function measured by turbidimetric platelet aggregation. 3. Short term infusion of adrenoceptor agonists with α 2 activity caused reductions in the platelet response to adrenaline in vitro ; conversely an increase in activity was observed postoperatively in two patients after removal of phaeochromocytoma. 4. The changes in platelet response were not accompanied by changes in α 2 -adrenoceptor number. 5. It is proposed that a process of receptor inactivation occurs during desensitization and this is responsible for the dynamic regulation of platelet responses.

1. The relationship between α-adrenoceptor number and response has been studied in rabbits under a range of physiological and pathological conditions. 2. The effects of irreversible α-adrenoceptor blockade, maturation, ageing, oestrogen treatment, adrenaline infusion, perinephritis hypertension and sinoaortic denervation on α-adrenoceptor number and response were examined. 3. α-Adrenoceptor number was measured by radioligand binding. [ 3 H]Prazosin and [ 3 H]clonidine were used as ligands to measure α 1 - and α 2 -adrenoceptor number in spleen and [ 3 H]yohimbine to measure α 2 -adrenoceptor number on platelets. Responses in vivo were studied by examining the pressor responses to a range of α-adrenoceptor agonists. The functional response of platelets was examined in vitro by using the aggregatory response to adrenaline. 4. Reductions in α 2 -adrenoceptor ligand binding were consistently accompanied by equivalent reductions in α 2 -adrenoceptor-mediated responses. In contrast large reductions in [ 3 H]prazosin binding were observed with little or no change in α 1 -adrenoceptor-mediated responses. 5. These results would be consistent with a large receptor reserve for α 1 -adrenoceptors but few if any spare α 2 -adrenoceptors in the vasculature or on platelets. 6. Increased responses to both α 1 - and α 2 -adrenoceptor agonists were observed in animals with sinoaortic denervation and to α 1 -adrenoceptor agonists in rabbits with perinephritis hypertension. These increases in response were not accompanied by increases in radioligand binding and may be related to alterations in the coupling of receptor activation to end-organ response.