Salvia divinorum , whose main active ingredient is the neoclerodane diterpene Salvinorin A, a hallucinogenic plant in mint family that has been used traditional spiritual practices for its psychoactive properties by Mazatecs of Oaxaca, Mexico. More recently, S. extracts and A have become more widely U.S. as legal hallucinogens. We discovered potently selectively inhibited 3 H-bremazocine binding to cloned κ opioid receptors. had no significant activity against battery 50 receptors,...

National and international health organizations have focused increasingly on a perceived obesity epidemic said to pose drastic threats public health. Indeed, some medical experts gone so far as predict that growing body mass will halt perhaps even reverse the millennia-long trend of rising human life expectancy. 1 In response such concerns agencies across world sprung into action, searching for policies or incentives mitigate alleged ‘disease’ obesity. Yet volume alarm grows louder, number...

The rostral ventrolateral medulla is the primary site of action for clonidine, a centrally acting antihypertensive. In medulla, clonidine binds not only to alpha-2 adrenergic receptors but also specific imidazole sites. order determine whether putative receptor mediates hypotensive series compounds was tested 1) in vitro binding affinity at and sites 2) vivo ability lower arterial pressure heart rate when microinjected directly into medulla. Hypotensive potency correlated with (r = 0.84),...

Both the hypotension and sedation elicited by centrally acting antihypertensive agents are traditionally attributed to activation of alpha 2 adrenergic receptors. Second-generation such as moxonidine less sedating but retain efficacy. A novel receptor which recognizes imidazolines may contribute their vasodepressor action in ventrolateral medulla (VLM). We sought determine whether was a selective ligand for these putative I1-imidazoline receptors different species tissues. Moxonidine...

Summary: Both the hypotension and sedation elicited by centrally acting antihypertensive agents traditionally are ascribed to activation of α2-adrenergic receptors. However, second-generation such as moxonidine rilmenidine less sedating but retain efficacy. The vasodepressor action clonidine within its brainstem site in ventrolateral medulla has been linked a novel receptor that recognizes imidazoles related compounds. We sought characterize interactions with these putative I1-imidazoline...

Nonadrenergic imidazoline receptors (I receptors) mediate the central antihypertensive effects of clonidine. Agmatine, an arginine metabolite that is synthesized within bovine brain and exhibits clonidine-displacing substance (CDS) activity, might be endogenous I receptor neurotransmitter. The authors compared affinity agmatine versus potency hypothalamic CDS, at adrenomedullary I1 human clonidine-binding sites: alpha-2A, alpha-2B alpha-2C expressed on transfected cell lines, sites platelet...

Fatty acids are the primary fuel for heart and ligands peroxisome proliferator-activated receptors (PPARs), which regulate expression of genes encoding proteins involved in fatty acid metabolism. Saturated acids, particularly palmitate, can be converted to proapoptotic lipid intermediate ceramide. This study assessed cardiac function, PPAR-regulated genes, cardiomyocyte apoptosis rats after 8 wk on either a low-fat diet [normal chow control (NC); 10% fat calories] or high-fat diets composed...

We sought to determine the site of action and receptor type responsible for antihypertensive actions rilmenidine. an oxazoline analogue clonidine. In anesthetized paralyzed rats decerebration did not alter dose dependent reductions in arterial pressure heart rate elicited by i.v. drug. Rilmenidine microinjected bilaterally into C1 area rostral ventrolateral medulla (RVL), but nucleus tractus solitarii (NTS) nor caudal (CVL), dose-dependent falls at doses order magnitude less than required...

Summary: The rostral ventrolateral medulla (RVLM) is the primary region maintaining vasomotor tone, and a site of action for central antihypertensive agents. In vitro [125I]p-iodoclonidine binding studies showed that moxonidine was selective I1-imidazoline over α2-adrenergic receptors in RVLM. We identified efaroxan SK&F 86466 as I1- α2-antagonists, respectively. tested moxonidine's within RVLM spontaneously hypertensive rats (SHRs) on or receptors, determined whether mediates systemic...

In anesthetized, paralyzed rats intravenous administration of the acetylcholinesterase inhibitor physostigmine (PHY) (100 micrograms/kg) evoked a dose-related rise in arterial pressure (AP) and heart rate (HR) an associated increase sympathetic nerve activity (SNA). The responses to PHY were blocked by electrolytic lesions of, or microinjection kainic acid into, specific site rostral ventrolateral medulla containing cluster neurons immunoreactive for adrenaline-synthesizing enzyme...

Moderate hyperhomocysteinemia is associated with several diseases, including coronary artery disease, stroke, Alzheimer9s schizophrenia, and spina bifida. However, the mechanisms for their pathogenesis are unknown but could involve interaction of homocysteine or its metabolites molecular targets such as neurotransmitter receptors, channels, transporters. We discovered that l-homocysteine sulfinic acid (l-HCSA),l-homocysteic acid, l-cysteine l-cysteic potent effective agonists at rat...

The effects of dietary fat intake on the development left ventricular hypertrophy and accompanying structural molecular remodeling in response to hypertension are not understood. present study compared a high-fat versus low-fat diet hypertrophy, remodeling, contractile dysfunction, induction markers (ie, expression mRNA for atrial natriuretic factor myosin heavy chain beta). Dahl salt-sensitive rats were fed either (10% total energy from fat) or (60% low-salt high-salt (6% NaCl) chow 12...

The selective angiotensin (ANG II) antagonists losartan (DuP 753) and PD 123319 have been shown to bind selectively AT1 AT2 subtypes, respectively. To characterize ANG II receptor subtypes in mesangial cells, washed membranes were incubated with 0.1 0.5 nM 125I-ANG increasing concentrations of competitors. inhibition binding by was biphasic, LIGAND curve-fitting analysis revealed two populations specific sites. One subpopulation comprised 86% the total showed high affinity for losartan, but...