Beta3-adrenergic receptors--studies on rainbow trout reveal ancient evolutionary origins and functions distinct from the thermogenic response.

نویسنده

  • Mikko Nikinmaa
چکیده

FOR MOST PHYSIOLOGISTS it is clear that the major function for 3-adrenergic receptors is to mediate metabolic and thermogenic responses in adipose tissue (12). Thus one would expect their distribution to be restricted to homeothermic animals. However, in this issue of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Nickerson et al. (5) report the presence of two different 3-adrenergic receptors in the tissues of a teleost fish, rainbow trout. In evolutionary terms, this means that 3-receptor has differentiated from other -adrenergic receptors before the division of teleost and tetrapod lineages that is estimated to have happened 350–400,000,000 years ago (2). Also, the presence of 3-adrenergic receptors in the cells of teleost fish indicates that this receptor subtype has important functions independent of the thermogenic response. Although the functions of the 3-adrenergic receptor subtype found in the heart and gill tissues were not clarified, detailed studies by Nickerson and coworkers (5) indicate that the red blood cell type 3-adrenergic receptor controls the function of adrenergically regulated sodium/proton exchange present in the erythrocytes of teleost fish. The physiological role of adrenergic stimulation of sodium/proton exchange in teleost fish has been clarified, as detailed below, but the adrenergic receptors involved have remained uncharacterized until now. Pharmacological studies suggested that the receptor subtype involved could be 1 (14). However, on the basis of earlier studies and those of Nickerson et al. (5), the mammalian pharmacological classification does not fit the teleost receptors. Thus the molecular characterization of the receptor with unique pharmacological properties is a significant step forward also in this regard. With regard to the physiological role of the 3-adrenergic receptor in teleost erythrocytes, in the early 1980s it was discovered that catecholamines (epinephrine and norepinephrine) could very rapidly increase the hemoglobin-oxygen affinity as a result of an increase in erythrocyte pH (6, 7). The increase in erythrocyte pH was shown to be due to -adrenergic activation of sodium/proton exchange across the erythrocyte membrane (1, 10), using cAMP as a second messenger (4). The adrenergic response augments oxygen transport by increasing erythrocyte pH when oxygen availability in ambient water is reduced (13) and protects oxygen loading in gills in exhaustive exercise by maintaining erythrocyte pH when blood plasma is acidified (9, 11). The erythrocyte response to catecholamines presents a new type of stress response that is observed in physiological conditions in many teleost fishes, but not in cyclostomes, most amphibians, birds, or mammals (8). In birds, another ion transport pathway, the sodium/potassium/2 chloride cotransport (3), is -adrenergically activated. Interestingly, the -receptor subtype of bird erythrocyte membrane, termed 4, also belongs to the 3-adrenergic receptor family. Thus, because effects on ion transport occur in evolutionarily distant species, it is tempting to speculate that the initial function of 3-receptor is related to ion transport. The study by Nickerson et al. (5) shows the strengths of comparative physiology: experiments on teleost fish shed light on both the evolution and the initial functions of a receptor, which has evolved to a very specific system in homeothermic mammals. Clearly, as indicated by the present studies, a combination of molecular methodology and the comparative approach is a very useful tool for future investigations of physiological regulation.

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عنوان ژورنال:
  • American journal of physiology. Regulatory, integrative and comparative physiology

دوره 285 3  شماره 

صفحات  -

تاریخ انتشار 2003