PK11195, a ligand of peripheral-type benzodiazepine receptor can stimulate thealdosterone secretion of isolated adrenal glomerulosa cell: this effect could be abolished by nifedipinewhich mainly blocks the calcium cha...PK11195, a ligand of peripheral-type benzodiazepine receptor can stimulate thealdosterone secretion of isolated adrenal glomerulosa cell: this effect could be abolished by nifedipinewhich mainly blocks the calcium channel in plasma membrane, but could not be abolished bydantrolene, a selective blocker of mitochondria calcium channel. Even under the condition of themaximum stimulative effects on aldosterone secretion, PK11195 could not change the cyclic AMP（cAMP） content in isolated glomerulosa cells. These results indicated that in the modulatory mecha-nism of benzodiazepine receptor on aldosterone secretion, the intracellular messenger might be theCa<sup>2+</sup> from extracellular Ca<sup>2+</sup> pool, but not the Ca<sup>2+</sup> from mitochondria Ca<sup>2+</sup> pool or cAMP.展开更多
Obesity is increasingly prevalent worldwide,with genetic factors contributing to its development.The hypothalamic leptin-melanocortin pathway is central to the regulation of appetite and weight;leptin activates the pr...Obesity is increasingly prevalent worldwide,with genetic factors contributing to its development.The hypothalamic leptin-melanocortin pathway is central to the regulation of appetite and weight;leptin activates the proopiomelanocortin neurons,leading to the production of melanocortin peptides;these in turn act on melanocortin 4 receptors(MC4R)which suppress appetite and increase energy expenditure.MC4R mutations are responsible for syndromic and non-syndromic obesity.These mutations are classified based on their impact on the receptor's life cycle:i.e.null mutations,intracellular retention,binding defects,signaling defects,and variants of unknown function.Clinical manifestations of MC4R mutations include early-onset obesity,hyperphagia,and metabolic abnormalities such as hyperinsulinemia and dyslipidemia.Management strategies for obesity due to MC4R mutations have evolved with the development of targeted therapies such as Setmelanotide,an MC4R agonist which can reduce weight and manage symptoms without adverse cardiovascular effects.Future research directions must include expansion of population studies to better understand the epidemiology of MC4R mutations,exploration of the molecular mechanisms underlying MC4R signaling,and development of new therapeutic agents.Understanding the interaction between MC4R and other genetic and environmental factors will be key to advancing both the prevention and treatment of obesity.展开更多
文摘PK11195, a ligand of peripheral-type benzodiazepine receptor can stimulate thealdosterone secretion of isolated adrenal glomerulosa cell: this effect could be abolished by nifedipinewhich mainly blocks the calcium channel in plasma membrane, but could not be abolished bydantrolene, a selective blocker of mitochondria calcium channel. Even under the condition of themaximum stimulative effects on aldosterone secretion, PK11195 could not change the cyclic AMP（cAMP） content in isolated glomerulosa cells. These results indicated that in the modulatory mecha-nism of benzodiazepine receptor on aldosterone secretion, the intracellular messenger might be theCa<sup>2+</sup> from extracellular Ca<sup>2+</sup> pool, but not the Ca<sup>2+</sup> from mitochondria Ca<sup>2+</sup> pool or cAMP.
文摘Obesity is increasingly prevalent worldwide,with genetic factors contributing to its development.The hypothalamic leptin-melanocortin pathway is central to the regulation of appetite and weight;leptin activates the proopiomelanocortin neurons,leading to the production of melanocortin peptides;these in turn act on melanocortin 4 receptors(MC4R)which suppress appetite and increase energy expenditure.MC4R mutations are responsible for syndromic and non-syndromic obesity.These mutations are classified based on their impact on the receptor's life cycle:i.e.null mutations,intracellular retention,binding defects,signaling defects,and variants of unknown function.Clinical manifestations of MC4R mutations include early-onset obesity,hyperphagia,and metabolic abnormalities such as hyperinsulinemia and dyslipidemia.Management strategies for obesity due to MC4R mutations have evolved with the development of targeted therapies such as Setmelanotide,an MC4R agonist which can reduce weight and manage symptoms without adverse cardiovascular effects.Future research directions must include expansion of population studies to better understand the epidemiology of MC4R mutations,exploration of the molecular mechanisms underlying MC4R signaling,and development of new therapeutic agents.Understanding the interaction between MC4R and other genetic and environmental factors will be key to advancing both the prevention and treatment of obesity.
