In vivo interactions between beta-1 and beta-2 adrenoceptors regulate catecholamine tachyphylaxia in human adipose tissue.
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.
Karolinska Institute, Department of Medicine and Research Center, Huddinge Hospital, Sweden.
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Arner
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Kriegholm
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Engfeldt
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D002395:Catecholamines / Q000378:metabolism*; D005260:Female; D005990:Glycerol / Q000378:metabolism*; D006801:Humans; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013618:Tachyphylaxis
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D005990:Glycerol