The Growth of Brown Adipose Tissue in Cold-acclimatized Rats after Depletion of Mast Cell Histamine by Compound 48/80

Abstract

Cold acclimatization (4-5°C) is accompanied by 2-3 fold increase of brown adipose tissue (BAT).This rapid growth of interscapular BAT was studied after histamine depletion. In control rats maintained at room temperature (28 ± 2°C) the BAT histamine content was 23.4 ± 5.9 (mean ± SD) Homeothermic animals have the capacity to maintain body temperature by a variety of physiological responses, the most important of which is to enhance nonshivering thermogenesis (NST). The rapid growth of the brown adipose tissue (BAT) appears to play a crucial role in NST and is thought to be mainly regulated by sympathetic noradrenaline (Rothwell & Stock 1985, Géloën et al. 1992 as well as other hormonal factors like thyroidal, adrenocortical and pancreatic hormones (Kuroshima et al. 1984, Howland & Bond 1987.Neurotransmitters that promote cell proliferation may do so by inhibiting adenylcyclase or by activating phospholipase C (PLC); these include 5-HT, adenosine (A1 receptors), norepinephrine (alpha-adrenergic receptors) and acetylcholine (muscarinic receptors) (for review see Lauder 1993). There are several reports that elevated level of histamine and its synthesizing enzyme are associated with rapid tissue growth (Kahlson & Rosengren 1968 Although the role of histamine in thermoregulation in the mammalian brain has been the focus of a number of investigations (Schwartz et al. 1991), no data exist in relation to the possible participation of histamine in promoting the hyperplasia of BAT in nonhibernating mammals submitted to acclimatization. The aim of this study was to determine whether normal growth of BAT takes place under condition of histamine depletion by compound 48/80. MATERIALS AND METHODSAdult female Sprague Dawley rats weighing 180-200 g raised in the Animal Facilities of Centroccidental University, were used. Each animal was caged separately and fed with commercial rat pellets. Four groups of animals were randomly chosen. Group A was kept at room temperature (28 ± 2°C) as well as group B, but the latter was pretreated with compound 48/80. Groups C and D were acclimatized at 5 ±1°C for a period of 20 days, but C was pretreated with compound 48/80.Depletion of histamine -The histamine-liberator compound 48/80 (Sigma, St. Louis, MO) was dissolved in 0.85% saline and injected intraperitoneally (i.p.) at an initial dose of 1 mg/kg. The following day the dose was increased to 2 mg/kg; two days later animals were injected with 3 mg/kg and three days later with 4 mg/kg until a dose of 5 mg/ kg was reached the 11th day. This chronic dosage of 5 mg/kg was continued every 5 days for 1 month. Treatment regime was maintained during the 20