Matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of MMPs (TIMPs), are produced in the gastrointestinal tract by several structural cells. The balance between MMPs and TIMPs is essential for many physiological processes in the gut. However, imbalance between MMPs and TIMPs plays an important role in the pathophysiology of diverse intestinal inflammatory conditi...

The 2C-adrenergic receptor ( 2CAR) is known to be poorly trafficked to the cell surface when expressed in a variety of cell types. We tested the hypothesis that the surface expression and signaling of 2CAR might be enhanced by heterodimerization with other G protein-coupled receptors (GPCRs). Cotransfection of 2CAR with more than 25 related GPCRs revealed that only coexpression with the 2-adren...

We kinetically analyzed the disposition of L-carnitine of juvenile visceral steatosis (JVS) mice compared with that of normal mice to elucidate the mechanism of the systemic L-carnitine deficiency of JVS mice. There were significant differences in the plasma concentration-time course of total radioactive carnitine (L-[H]carnitine, [acetyl-H]carnitine, and other [acyl-H]carnitines) between norma...

Age-related changes in the capacity, rate, and modulation of dopamine (DA) uptake within the striatum and the nucleus accumbens core of Fischer 344 rats were investigated using in vivo electrochemical recordings coupled with local drug application techniques. Equimolar amounts of DA were pressure ejected into the striatum and the nucleus accumbens of 6-, 12-, 18-, and 24-month old rats. The DA ...

The zinc-binding protein metallothionein (MT) is associated with resistance to apoptosis. We examined whether MT regulates the zinc-dependent antiapoptotic transcription factor nuclear factor B (NFB), which is up-regulated under many conditions that lead to elevated MT expression. NFB protein levels and NFB-dependent reporter gene activity were examined in clonal MT( ) (MT-WT) and MT( ) (MT-KO)...

We tested the hypothesis that an abnormal function of K channels in vascular smooth muscle cells plays a key role in the impaired acetylcholine (ACh) vasodilation in aortas from two kidney-one clip (2K-1C) hypertensive rats and further investigated the K channel subtype involved in this altered response. ACh-induced endothelium-dependent relaxation was assessed in aortic rings from 2K-1C and no...

In addition to their central role in ATP synthesis, mitochondria play a critical role in cell death. Oxidative stress accompanied by calcium overload, ATP depletion, and elevated phosphate levels induces mitochondrial permeability transition (MPT) with formation of nonspecific MPT pores (MPTP) in the inner mitochondrial membrane. Pore opening results in mitochondrial dysfunction with uncoupled ...

Repeated administration of morphine is associated with the development of tolerance, yet the mechanism underlying this phenomenon is still poorly understood. Recent evidence implicating glycogen synthase kinase 3 (GSK3) in opioid receptor signaling pathways has prompted us to investigate its role in morphine tolerance. Administration of 10 mg/kg morphine i.p. to Wistar rats twice daily for 8 da...

We recently reported an involvement of peripheral angiotensin II (ANG II) in the development of both the fever and the peripheral interleukin (IL)-1 production induced in rats by a systemic injection of lipopolysaccharide (LPS). The present study was performed to investigate whether brain ANG II contributes to the fever and IL-1 production in the rat brain induced by i.c.v. injection of LPS. LP...

Although intravenous administration of [D-penicillamine]enkephalin (DPDPE) produces significant antinociception in rodents, the duration of antinociception is short (;15 min). The present study was conducted to test the hypothesis that duration of antinociception for DPDPE is determined by both systemic and regional disposition (i.e., blood-brain translocation), and that the magnitude of antino...