kwic
changes
changes
right
off
ON
2
1
100
500
strict
ELIZA cgi-bash version rev. 1.91
- Medical English LInking keywords finder for the PubMed Zipped Archive (ELIZA) -
return
kwic search for changes out of >500 occurrences
332920 occurrences (No.57 in the rank) during 5 years in the PubMed. [no cache] 500 found
--- ABSTRACT ---
--- ABSTRACT END ---
[frequency of next (right) word to changes]
332920 occurrences (No.57 in the rank) during 5 years in the PubMed. [no cache] 500 found
| 2) Changes in core body temperature are fundamental and universal factors of mammalian life. |
| PMID:34158361 DOI:10.1124/molpharm.121.000309 |
| 2021 Molecular pharmacology |
| * Physiological Temperature Changes Fine-Tune β 2- Adrenergic Receptor-Induced Cytosolic cAMP Accumulation. |
| - Norepinephrine (NE) controls many vital body functions by activating adrenergic receptors (ARs). Average core body temperature (CBT) in mice is 37°C. Of note, CBT fluctuates between 36 and 38°C within 24 hours, but little is known about the effects of CBT changes on the pharmacodynamics of NE. Here, we used Peltier element-controlled incubators and challenged murine hypothalamic mHypoA -2/10 cells with temperature changes of ±1°C. We observed enhanced NE-induced activation of a cAMP-dependent luciferase reporter at 36 compared with 38°C. mRNA analysis and subtype specific antagonists revealed that NE activates β 2- and β 3-AR in mHypoA-2/10 cells. Agonist binding to the β 2-AR was temperature insensitive, but measurements of cytosolic cAMP accumulation revealed an increase in efficacy of 45% ± 27% for NE and of 62% ± 33% for the β 2-AR-selective agonist salmeterol at 36°C. When monitoring NE-promoted cAMP efflux, we observed an increase in the absolute efflux at 36°C. However, the ratio of exported to cytosolic accumulated cAMP is higher at 38°C. We also stimulated cells with NE at 37°C and measured cAMP degradation at 36 and 38°C afterward. We observed increased cAMP degradation at 38°C, indicating enhanced phosphodiesterase activity at higher temperatures. In line with these data, NE-induced activation of the thyreoliberin promoter was found to be enhanced at 36°C. Overall, we show that physiologic temperature changes fine-tune NE-induced cAMP signaling in hypothalamic cells via β 2-AR by modulating cAMP degradation and the ratio of intra- and extracellular cAMP. SIGNIFICANCE STATEMENT: Increasing cytosolic cAMP levels by activation of G protein-coupled receptors (GPCR) such as the β 2-adrenergic receptor (AR) is essential for many body functions. Changes in core body temperature are fundamental and universal factors of mammalian life. This study provides the first data linking physiologically relevant temperature fluctuations to β 2-AR-induced cAMP signaling, highlighting a so far unappreciated role of body temperature as a modulator of the prototypic class A GPCR. |
[
right
kwic]
(1)246  in |
(8)6 are |
(15)3 during |
(22)2 may |
| (2)35 *null* | (9)6 on |
(16)3 induced |
(23)2 observed |
| (3)29 of |
(10)5 after |
(17)3 the |
(24)2 occurring |
| (4)24 to |
(11)4 associated |
(18)3 throughout |
(25)2 required |
| (5)20 and |
(12)4 at |
(19)2 by |
(26)2 using |
| (6)11 were |
(13)4 within |
(20)2 could |
|
| (7)9 that |
(14)3 between |
(21)2 have |
add keyword
--- WordNet output for changes ---