This report describes the synthesis of [11C]2-(1-methyl-4-piperidinyl)-6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-3(2H)-pyridazinone ([11C]FR194921), a highly selective, nonxanthine-type adenosine A(1) receptor antagonist, used in brain imaging in rats and conscious monkeys as a potential novel PET tracer. [11C]FR194921 was successfully synthesized in 19 min after [11C]CH3I formation. The radiochemical yield was 38+/-3%; and radioactivity was 4.1+/-0.4 GBq, calculated from end of synthesis; radiochemical purity was higher than 99%; and the specific radioactivity was 25.0+/-8.1 GBq micromol(-1) (n=5). In a rat experiment, the distribution of [11C]FR194921 was higher in the hippocampus, striatum and cerebellum regions. This accumulation was significantly decreased by approximately 50% by pretreatment with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A1 receptor antagonist, which indicated specific binding of the radioligand to adenosine A1 receptors. In conscious monkey PET experiments, [11C]FR194921 accumulated in several regions of the brain, especially in the occipital cortex, thalamus and striatum. These results suggest that [11C]FR194921 can be used as an agent for imaging adenosine A1 receptors in vivo by positron emission tomography (PET).
Netrin-1, an essential extracellular protein, has gained significant attention due to its pivotal role in guiding axon and cell migration during embryonic development. The fundamental significance of netrin-1 in developmental biology is reflected in its high conservation across different species as a part of the netrin family. The bifunctional nature of netrin-1 demonstrates its functional versatility, as it can function as either a repellent or an attractant according to the context and the expressed receptors on the target cells including the deleted in colorectal cancer (DCC), the uncoordinated-5 (UNC5), DSCAM, Neogenin-1, Adenosine A2b and Draxin receptors.
Introduction: Acute coronary syndrome (ACS) patients undergoing primary percutaneous coronary intervention (PPCI) often experience the no-reflow phenomenon (NRP), characterized by reduced myocardial perfusion despite an open coronary artery. Adenosine, a potent vasodilator, is used to aid reperfusion. To elucidate underlying molecular mechanism of this phenomenon, we investigated expression of ADORA2A and ADORA2B genes, encoding adenosine receptors, in ACS patients with NRP and non-NRP.
Activation of PLCβ enzymes by G and G proteins is a common mechanism to trigger cytosolic Ca increase. We and others reported that G inhibitor FR900358 (FR) can inhibit both and G - and, surprisingly, G -mediated intracellular Ca mobilization. Thus, the G -G -PLCβ-Ca signaling axis depends entirely on the presence of active G , which reasonably explained FR-inhibited G -induced Ca release.
Insect gustatory receptors play a critical role in modulating feeding behaviors by detecting external nutritional cues through complex biochemical pathways. Bitter taste receptors are essential for insects to identify and avoid toxins. However, the detailed molecular and cellular mechanisms by which these receptors influence insect feeding behavior remain poorly understood.
Objective: To explore the protective effect and mechanism of acetate on sepsis-induced acute kidney injury (AKI) in rats.
Methods: Male Sprague-Dawley (SD) rats were divided into sham operation group (Sham group), sepsis group caused by cecal ligation and puncture (CLP group), and acetate pretreatment group [NaA group, gavage sodium acetate (NaA) 300 mg/kg twice a day for 7 consecutive days before CLP] using a random number table method, with 7 rats in each group. The blood was taken from the main abdominal artery 24 hours after modeling, and renal tissue was collected from the rats.
