We investigated, in 36 healthy volunteers, the effects of prednisone and ketotifen on recovery of lymphocyte j2-adrenoceptor density (determined by (-)-'"iodocyanopindolol binding) and responsiveness (assessed by lymphocyte cyclic AMP IcAMPI responses to 10 AtM (-)-isoprenaline) after desensitization by the p2-agonist terbutaline. Terbutaline (3 X 5 mg/d) decreased lymphocyte #2-adrenoceptor density by -40-50%; concomitantly, lymphocyte cAMP responses to 10 ,gM (-)-isoprenaline were significantly reduced. After withdrawal of terbutaline 2-adrenoceptor, density and responsiveness gradually increased, reaching predrug levels after 4 d.Prednisone (1 X 100 mg orally) accelerated ,f2-adrenoceptor recovery; only 8-10 h after administration of the steroid ,62-adrenoceptor density and cAMP responses to (-)-isoprenaline had reached values not significantly different from pretreatment levels. Similar effects were obtained with ketotifen (2 mg; thereafter 2 X 1 mg/d for 4 d): 24 h after application of the drug (32-adrenoceptor density and cAMP responses to (-)-isoprenaline had reached pretreatment levels. Furthermore, ketotifen simultaneously applied with terbutaline completely prevented terbutaline-induced decrease in lymphocyte i2-adrenoceptor density and responsiveness. Prednisone (1 X 100 mg orally) or ketotifen (2 mg; thereafter 2 X 1 mg/d for 2 d) had no significant influence on lymphocyte #2-adrenoceptor density in healthy volunteers not pretreated with terbutaline, but shifted the ratio high-to-low affinity state of the lymphocyte j#2-adrenoceptor toward high affinity state.We conclude that glucocorticoids as well as ketotifen can accelerate recovery of density and responsiveness of lymphocyte B2-adrenoceptors desensitized by long-term treatment with 2-agonists. Such an effect may have clinical implications for preventing tachyphylaxis of asthmatic patients against therapy with 02-agonists.

In the present study the effects of pindolol [non-selective beta-adrenoceptor antagonist with strong partial agonistic activity (PAA)] on beta 2-adrenoceptor density in lymphocytes (assessed by (-)-[125I]iodocyanopindolol (ICYP) binding) were compared with those of the beta 1-selective antagonists celiprolol (with PAA) and bisoprolol (no PAA) in normotensive young volunteers to get further insights into the nature of PAA. Administration of pindolol (2 X 5 mg/day) caused an about 25% decrease in lymphocyte beta 2-adrenoceptor density after 2 days; during treatment beta 2-adrenoceptor density declined further (maximum decrease after 7 days: 50%). After withdrawal of pindolol lymphocyte beta 2-adrenoceptor density recovered very slowly being still after 4 days significantly reduced, although no pindolol was detectable in plasma after 36 h. The KD-values for ICYP, however, did not change during or after pindolol treatment. The decrease in lymphocyte beta 2-adrenoceptor density induced by pindolol could be completely prevented by simultaneous administration of propranolol (3 X 40 mg/day) indicating that the PAA of pindolol is the cause of its beta-adrenoceptor decreasing effect. Administration of the non-selective beta-adrenoceptor antagonist bopindolol (1 X 2 mg/day) with PAA caused decreases in lymphocyte beta 2-adrenoceptor density (maximum decrease after 7 days: 40%); concomitantly the 10 mumol/l (-)-isoprenaline evoked increases in the intracellular level of lymphocyte cyclic AMP were attenuated to a similar extent indicating that the beta-adrenoceptor antagonist-induced decrease in beta-adrenoceptor density is accompanied by a loss in beta-adrenoceptor function.(ABSTRACT TRUNCATED AT 250 WORDS)

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