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Salvia divinorum, whose main active ingredient is the neoclerodane diterpene Salvinorin A, is a hallucinogenic plant in the mint family that has been used in traditional spiritual practices for its psychoactive properties by the Mazatecs of Oaxaca, Mexico. More recently, S. divinorum extracts and Salvinorin A have become more widely used in the U.S. as(More)
As a result of superior efficacy and overall tolerability, atypical antipsychotic drugs have become the treatment of choice for schizophrenia and related disorders, despite their side effects. Weight gain is a common and potentially serious complication of some antipsychotic drug therapy, and may be accompanied by hyperlipidemia, hypertension and(More)
The identification of protein function based on biological information is an area of intense research. Here we consider a complementary technique that quantitatively groups and relates proteins based on the chemical similarity of their ligands. We began with 65,000 ligands annotated into sets for hundreds of drug targets. The similarity score between each(More)
Insulin resistance is associated with both obesity and hypertension. However, the cellular mechanisms of insulin resistance in genetic models of obese-hypertension have not been identified. The objective of the present study was to investigate the effects of genetic obesity on a background of inherited hypertension on initial components of the insulin(More)
Data were presented showing that I1-imidazoline sites show a unique ligand specificity that differs markedly from that of any of the alpha 2-adrenergic subtypes or the I2-imidazoline sites labeled by [3H]idazoxan. On the other hand, the ligand specificity of I1-imidazoline sites is maintained across mammalian species (cow, rat, dog, and human) and between(More)
Fatty acids are the primary fuel for the heart and are ligands for peroxisome proliferator-activated receptors (PPARs), which regulate the expression of genes encoding proteins involved in fatty acid metabolism. Saturated fatty acids, particularly palmitate, can be converted to the proapoptotic lipid intermediate ceramide. This study assessed cardiac(More)
OBJECTIVE To review previous work and present additional evidence characterizing the I1-imidazoline receptor and its role in cellular signaling, central cardiovascular control, and the treatment of metabolic syndromes. Second-generation centrally-acting antihypertensives inhibit sympathetic activity mainly via imidazoline receptors, whereas first-generation(More)
We sought to further elucidate signal transduction pathways for the I1-imidazoline receptor in PC12 cells by testing involvement of protein kinase C (PKC) isoforms (betaII, epsilon, zeta), and the mitogen-activated protein kinases (MAPK) ERK and JNK. Stimulation of I1-imidazoline receptor with moxonidine increased enzymatic activity of the classical betaII(More)
The I1-imidazoline receptor is expressed in the rostral ventrolateral medulla (RVLM) where it mediates vasodepression, and in PC12 pheochromocytoma cells where it elicits generation of diacylglycerol independent of phosphatidylinositol turnover or activation of phospholipase D. We hypothesized that the I1-imidazoline receptor couples to a(More)
The rostral ventrolateral medulla is the primary site of action for clonidine, a centrally acting antihypertensive. In the rostral ventrolateral medulla, clonidine binds not only to alpha-2 adrenergic receptors but also to specific imidazole sites. In order to determine whether a putative imidazole receptor mediates the hypotensive action of clonidine, a(More)