The biological effects of steroid hormones are mediated by receptors associated with the plasma membrane as well as located inside of target cells. This perspective focuses on recent advances in our understanding of the integration that occurs between membrane-associated rapid signaling events and various changes in gene transcription that modulate the function and phenotype of steroid-responsi...

The enzyme cyclooxygenase (COX) catalyzes the first step of the synthesis of prostanoids. In the early 1990s, COX was demonstrated to exist as two distinct isoforms. COX-1 is constitutively expressed as a “housekeeping” enzyme in most tissues. By contrast, COX-2 can be up-regulated by various proinflammatory agents, including lipopolysaccharide, cytokines, and growth factors. Whereas many of th...

The -aminobutyric acid type C (GABAC) receptor is structurally related to the GABAA receptors, yet quite distinct physiologically and pharmacologically. Neuroactive steroids are known to be potent and efficacious modulators of the GABAA receptor, but they are less well characterized in their actions on the GABAC receptor. We have examined the actions of neuroactive steroids and analogs on 1 (GA...

The present study provides evidence that inducible nitric-oxide synthase (iNOS)-mediated nitrative stress plays a pivotal role in chronic -adrenergic receptor (AR) stimulation-induced cardiac damage. In mice, 14 days of isoproterenol (ISO) stimulation via an osmotic minipump induced an up-regulation of iNOS as evidenced by increases in mRNA, protein expression, and immunochemical staining of my...

In this study, we explored the relationship between ligand-induced regulation of surface opioid receptors and G protein activation. G protein activation was assessed with [S]guanosine-5 -O-(3thio)triphosphate (GTP S) binding assays conducted at both 37 and 0°C. Ligand-independent (constitutive) activity of the -receptor was readily observed when the [S]GTP S binding assay was performed at 37°C....

Hydrogen sulfide (H2S) is enzymatically generated in mammalian tissues from either L-cysteine or L-homocysteine. H2S possesses multiple biological activities, including regulation of vascular tone and blood pressure. Hydrogen sulfide produced in endothelial cells, vascular smooth muscle cells, and perivascular adipose tissue dilates blood vessels by activating ATP-sensitive potassium channels. ...

During postnatal development, alpha-2 adrenergic receptors (A2AR) change in both density and distribution. In forebrain, receptor density increases about 4-fold over neonatal levels, reaching adult levels before postnatal day (P) 28, whereas in hindbrain, including cerebellum, there is a decrease in overall receptor density. We examined the coupling of A2AR to G proteins using agonist-stimulate...

The tumor suppressor protein p53 is currently a target of emerging drug therapies directed toward neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, and side effects associated with cancer treatments. Of this group of drugs, the best characterized is pifithrin, a small molecule that inhibits p53-dependent apoptosis through an undetermined mechanism. In this study, we have used a n...

We have demonstrated the effects of estrogen on modulation of ATP-sensitive K channels; however, the subcellular location of these channels is unknown. The purpose of the present study was to investigate the role of the sarcolemmal and mitochondrial ATP-sensitive K channels in a canine model of myocardial infarction after stimulation with 17 -estradiol. Anesthetized dogs were subjected to 60 mi...

Salvinorin A [(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2(3-furanyl)-dodecahydro-6a,10b-dimethyl-4,10-dioxo-2h-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester] is a hallucinogenic -opioid receptor agonist that lacks the usual basic nitrogen atom present in other known opioid ligands. Our first published studies indicated that Salvinorin A weakly inhibited -receptor binding, and subsequent e...