1.Adenosine protects Sprague Dawley rats from high-fat diet and repeated acute restraint stress-induced intestinal inflammation and altered expression of nutrient transporters.
Lee CY1. J Anim Physiol Anim Nutr (Berl). 2015 Apr;99(2):317-25. doi: 10.1111/jpn.12247. Epub 2014 Sep 6.
This study investigated the effect of repeated acute restraint stress and high-fat diet (HFD) on intestinal expression of nutrient transporters, concomitant to intestinal inflammation. The ability of adenosine to reverse any change was examined. Six-week-old male Sprague Dawley rats were divided into eight groups: control or non-stressed (C), rats exposed to restraint stress for 6 h per day for 14 days (S), control rats fed with HFD (CHF) and restraint-stressed rats fed with HFD (SHF); four additional groups received the same treatments and were also given 50 mg/l adenosine dissolved in drinking water. Fasting blood glucose, plasma insulin, adiponectin and corticosterone were measured. Intestinal expression of SLC5A1, SLC2A2, NPC1L1 and TNF-α was analysed. Histological evaluation was conducted to observe for morphological and anatomical changes in the intestinal tissues. Results showed that HFD feeding increased glucose and insulin levels, and repeated acute restraint stress raised the corticosterone level by 22%.
2.Upregulation of adenosine A1 receptors facilitates sinoatrial node dysfunction in chronic canine heart failure by exacerbating nodal conduction abnormalities revealed by novel dual-sided intramural optical mapping.
Lou Q1, Hansen BJ1, Fedorenko O1, Csepe TA1, Kalyanasundaram A1, Li N1, Hage LT1, Glukhov AV1, Billman GE1, Weiss R1, Mohler PJ1, Györke S1, Biesiadecki BJ1, Carnes CA1, Fedorov VV2. Circulation. 2014 Jul 22;130(4):315-24. doi: 10.1161/CIRCULATIONAHA.113.007086. Epub 2014 May 16.
BACKGROUND: Although sinoatrial node (SAN) dysfunction is a hallmark of human heart failure (HF), the underlying mechanisms remain poorly understood. We aimed to examine the role of adenosine in SAN dysfunction and tachy-brady arrhythmias in chronic HF.
3.Diadenosine diphosphate (Ap₂A) delays neutrophil apoptosis via the adenosine A2A receptor and cAMP/PKA pathway.
Pliyev BK1, Dimitrieva TV, Savchenko VG. Biochem Cell Biol. 2014 Oct;92(5):420-4. doi: 10.1139/bcb-2014-0059. Epub 2014 Jul 18.
Diadenosine polyphosphates have been shown to inhibit neutrophil apoptosis, but mechanisms of the antiapoptotic effect are not known. Diadenosine diphosphate (Ap2A) is the simplest naturally occurring diadenosine polyphosphate, and its effect on neutrophil apoptosis has not previously been investigated. Here we report that Ap2A delays spontaneous apoptosis of human neutrophils, and the effect is reversed by the adenosine A2A receptor antagonists SCH442416 and ZM241385. Ap2A induced an elevation of intracellular cAMP and the elevation was blocked by the adenosine A2A receptor antagonists. The antiapoptotic effect of Ap2A was abrogated by 2',5'-dideoxyadenosine, an inhibitor of adenylyl cyclase, and Rp-8-Br-cAMPS, an inhibitor of type I cAMP-dependent protein kinase A (PKA). Together, these results demonstrate that Ap2A delays neutrophil apoptosis via the adenosine A2A receptor and cAMP/PKA signaling axis.
4.Intrathecal baclofen, a GABAB receptor agonist, inhibits the expression of p-CREB and NR2B in the spinal dorsal horn in rats with diabetic neuropathic pain.
Liu P1, Guo WY, Zhao XN, Bai HP, Wang Q, Wang XL, Zhang YZ. Can J Physiol Pharmacol. 2014 Aug;92(8):655-60. doi: 10.1139/cjpp-2013-0463. Epub 2014 Jul 2.
This study aimed to investigate the effect of baclofen, a γ-aminobutyric acid B (GABAB) receptor agonist, on the expression of p-CREB and NR2B in the spinal dorsal horn of rats with diabetic neuropathic pain (DNP). The DNP rats, which were successfully induced with streptozocin, were distributed among 3 groups that were treated with saline (D1 group), baclofen (D2 group), or CGP55845 + baclofen (D3 group) continuously for 4 days. The rats induced with saline and subsequently treated with saline were used as controls (C group). The times for the paw withdrawal threshold and thermal withdrawal latency of the D1 group were lower than those for the C group, and were significantly increased after baclofen treatment, but not when GABA receptor was pre-blocked with CGP55845 (D3 group). Increased protein expression levels of NR2B and p-CREB and mRNA levels of NR2B were found in the D1 group when compared with the controls. Baclofen treatment significantly suppressed their expression, bringing it close to the levels of controls.