The tissue distribution of the human β3-adrenoceptor studied using a monoclonal antibody: Direct evidence of the β3-adrenoceptor in human adipose tissue, atrium and skeletal muscle

Abstract

The tissue distribution of the human b b 3 -adrenoceptor studied using a monoclonal antibody: Direct evidence of the b b 3 -adrenoceptor in human adipose tissue, atrium and skeletal muscle 2,3 The human b 3 -adrenoceptor was later cloned by Emorine et al. 4 The pharmacology of the cloned b 3 -adrenoceptor agreed with the pharmacological data previously obtained in rodent adipose tissue, gut, and skeletal muscle in that the badrenoceptors in these tissues were insensitive to classical b-adrenoceptor antagonists such as propranolol.5 ± 8 Aryloxypropanolamine b 1 ab 2 adrenoceptor antagonists, exempli®ed by CGP12177, evoke a lipolytic response in rat adipose tissue through agonism at b 3 -adrenoceptors. 9 Similarly, selective b 3 -adrenoceptor agonists, such as BRL-37344, showed similar or greater potency than isoproterenol in stimulating lipolysis, but were much less potent than isoproterenol in stimulating responses mediated by b 1 -or b 2 -adrenoceptors. 10 The assessment of the pharmacological role of b 3 -adrenoceptors in human tissues has proved more controversial. For example, lipolysis in human white adipocytes induced by isoproterenol is sensitive to propranolol.11 Also, CGP12177-induced lipolytic responses have been demonstrated by some 12 ± 14 but not others. 9,15 It is now evident from comparisons of cloned human and rat b 3 -adrenoceptors that there are signi®cant species differences in pharmacology. 16 Attempts to detect b 3 -mRNA in human tissues using reverse-transcription PCR have also given conicting results. Krief et al 17 detected b 3 -adrenoceptor mRNA in several tissues, including gall bladder, adipose tissue and colon, while Thomas and Liggett 18 failed to detect a b 3 -adrenoceptor signal. Recently, RNAase protection assays, that do not rely on ampli®cation techniques, were used to identify b 3 -adrenoceptor mRNA in a variety of human tissues, including

Distribution and quantification of β-3 adrenergic receptor in tissues of sheep

“…Generally, higher ADRB3 expression was found in deep deposits than in subcutaneous ones. This phenomenon is consistent with the studies in adult humans (Krief et al, 1993;Chamberlain et al, 1999).…”

“…Chamberlain et al (1999) andde Matteis et al (2002) demonstrated in humans (by immunohistochemistry) the existence of the ADRB3 protein in white adipocytes that came from subcutaneous fat and omental deposits. Likewise, as detected by both the RT-PCR of mRNA and immunohistochemistry techniques in this study, ADRB3 receptor was distributed in ovine subcutaneous, small and great omental, retroperitoneal, mesenteric and perirenal fat.…”

Attenuation of 3,4‐methylenedioxymethamphetamine (MDMA, Ecstasy)‐induced rhabdomyolysis with α1‐ plus β3‐adrenoreceptor antagonists

“…Although expressed in relatively low concentrations, skeletal muscle contains both a 1 AR (Martin et al, 1990) and b 3 AR (Sillence et al, 1993;Ye et al, 1995;Chamberlain et al, 1999). As UCP3 plays a major role in MDMA-induced hyperthermia , we suggest that part of the protective effects seen in the present study may be the result of a 1 AR-and b 3 ARdependent regulation of UCP3 activity in skeletal muscle.…”

Tools to study β3-adrenoceptors

“…This can be done both at the protein and the mRNA level. Although some β 3 -adrenoceptor antibodies have been reported (Chamberlain et al 1999) and are commercially available, to the best of our knowledge, none of them has been well validated and shown to display a useful selectivity for β 3 -adrenoceptors relative to other β-adrenoceptor subtypes or other receptors in general. Therefore, as with most G-proteincoupled receptors, detection of β 3 -adrenoceptors at the protein level is largely confined to radioligand binding studies.…”