Alpha 1- and beta-adrenergic regulation of intracellular Ca2+ levels in brown adipocytes.
In order to monitor changes in cytosolic Ca2+ levels, brown-fat cells were incubated with the fluorescent Ca2+-indicator fura-2 and the fluorescence intensity ratio followed. The addition of norepinephrine led to a rapid and persistent increase in the cytosolic Ca2+ level, which was dose-dependent with a maximal effect at about 1 microM. The response was diminished in the absence of extracellular Ca2+ and was inhibited more efficiently by phentolamine and prazosin than by propranolol or yohimbine, indicating alpha 1-adrenergic mediation. Accordingly, selective alpha 1-adrenergic stimulation also increased the cytosolic Ca2+ level. However, selective beta-adrenergic stimulation, as well as the adenylate cyclase activator forskolin, were also able to increase the cytosolic Ca2+ level in these cells to a certain extent. It was concluded that the major part of the increase in cytosolic Ca2+ was mediated, as in other cell types, via alpha 1-adrenergic receptors, but that Ca2+ levels were also positively modulated by a cAMP-mediated process. These observations are discussed in relation to known alpha 1/beta synergisms in brown adipose tissue.
Wilcke
M
M
Wenner-Gren Institute, Arrhenius Laboratories, University of Stockholm, Sweden.
Nedergaard
J
J
D002001:Adipose Tissue, Brown / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D003593:Cytoplasm / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000494:pharmacology; D016257:Fura-2; D066298:In Vitro Techniques; D015759:Ionomycin; D008345:Manganese / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001572:Benzofurans; D004987:Ethers; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D008345:Manganese; D015759:Ionomycin; D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine