In vivo interactions between beta-1 and beta-2 adrenoceptors regulate catecholamine tachyphylaxia in human adipose...

Catecholamine tachyphylaxia was investigated in human s.c. adipose tissue in situ by using microdialysis. The tissue was dialyzed with adrenergic agents (10(-8) mol/l) and the glycerol concentration (lipolysis index) was determined. Perfusion with adrenaline caused a 3-fold rise in the glycerol concentration, which peaked at 30 min and then (within 1 hr) declined to a level 75% higher than base line; the latter elevation was constant for at least 2 hr. Noradrenaline or isoprenaline in the absence and presence of a selective beta-2 receptor antagonist, or the selective beta-1 adrenergic agonist dobutamine, caused a 2- to 2.5-fold transient lipolytic response which also peaked at 30 min but then (within 3 hr) declined to the base-line level. On the other hand, isoprenaline plus a selective beta-1 receptor antagonist or the beta-2 selective adrenergic agonist terbutaline caused a constant lipolytic effect for at least 3 hr. Noradrenaline or adrenaline plus a nonselective beta adrenergic antagonist as well as the alpha-2 selective adrenergic antagonist clonidine caused a sustained antilipolytic action for at least 3 hr. In conclusion, the adrenoceptor subtypes involved in lipolysis regulation in humans have different in vivo sensitivities to homologous desensitization. Beta-2 and alpha-2 adrenoceptors are resistant in this respect whereas activation of beta-1 adrenoceptors leads to rapid desensitization. However, simultaneous beta-1 and beta-2 receptor activation is accompanied by different degrees of tachyphylaxia, indicating regulatory in vivo interactions within this receptor family in human adipose tissue.