Analysis of self-reported confidence in independent prescribing among osteopathic medical graduating seniors.

Context: Prescribing medications is one of the physicians' most important professional activities throughout their careers. Lack of confidence and competency to prescribe may lead to preventable medical errors. The prevalence of prescription errors among new graduate physicians has been widely studied.

Evaluation of an Educational Scholarship Fellowship Program for Health Professions Educators.

Introduction: Historically, the requirement to produce scholarship for advancement has challenged health professions educators heavily engaged in teaching. As biomedical scientists or healthcare practitioners, few are trained in educational scholarship, and related faculty development varies in scope and quality across institutions. Currently, there is a need for faculty development and mentoring programs to support the development of these skills.

Effects of Δ-Tetrahydrocannabinol and the Aminoalkylindole K2/Spice Constituent JWH-073 on Cardiac Tissue and Mesenteric Vascular Reactivity.

Although use of is not associated with serious adverse effects, recreational use of aminoalkylindole (AAI) cannabinoid receptor agonists found in K2/Spice herbal blends has been reported to cause adverse cardiovascular events, including angina, arrhythmia, changes in blood pressure, ischemic stroke, and myocardial infarction. Δ-Tetrahydrocannabinol (Δ-THC) is the primary CB agonist found in cannabis and JWH-073 is one of the AAI CB agonists found in K2/Spice brands sold to the public. This study used , , and approaches to investigate potential differences on cardiac tissue and vascular effects betweenJWH-073 and Δ-THC.

Design, synthesis, and evaluation of substituted alkylindoles that activate G protein-coupled receptors distinct from the cannabinoid CB and CB receptors.

The alkylindole (AI), WIN55212-2, modulates the activity of several proteins, including cannabinoid receptors 1 and 2 (CBR, CBR), and at least additional G protein-coupled receptor (GPCR) that remains uncharacterized with respect to its molecular identity and pharmacological profile. Evidence suggests that such AI-sensitive GPCRs are expressed by the human kidney cell line HEK293. We synthesized fourteen novel AI analogues and evaluated their activities at AI-sensitive GPCRs using [S]GTPγS and [H]WIN55212-2 binding in HEK293 cell membranes, and performed in silico pharmacophore modeling to identify characteristics that favor binding to AI-sensitive GPCRs versus CBR/CBR.

WIN55212-2 Modulates Intracellular Calcium via CB Receptor-Dependent and Independent Mechanisms in Neuroblastoma Cells.

The CB cannabinoid receptor (CBR) and extracellular calcium (eCa)-stimulated Calcium Sensing receptor (CaSR) can exert cellular signaling by modulating levels of intracellular calcium ([Ca]). We investigated the mechanisms involved in the ([Ca]) increase in N18TG2 neuroblastoma cells, which endogenously express both receptors. Changes in [Ca] were measured in cells exposed to 0.

Prolonged ethanol exposure modulates constitutive internalization and recycling of 5-HT1A receptors.

Alcohol exposure alters the signaling of the serotoninergic system, which is involved in alcohol consumption, reward, and dependence. In particular, dysregulation of serotonin receptor type 1A (5-HT1AR) is associated with alcohol intake and withdrawal-induced anxiety-like behavior in rodents. However, how ethanol regulates 5-HT1AR activity and cell surface availability remains elusive.

Cannabinoid receptor interacting protein 1a interacts with myristoylated Gα N terminus via a unique gapped β-barrel structure.

Cannabinoid receptor interacting protein 1a (CRIP1a) modulates CB cannabinoid receptor G-protein coupling in part by altering the selectivity for Gα subtype activation, but the molecular basis for this function of CRIP1a is not known. We report herein the first structure of CRIP1a at a resolution of 1.55 Å.

CB1 cannabinoid receptor-phosphorylated fourth intracellular loop structure-function relationships.

A peptide comprising the juxtamembrane C-terminal intracellular loop 4 (IL4) of the CB cannabinoid receptor possesses three Serine residues (Ser402, Ser411 and Ser415). Here we report the effect of Ser phosphorylation on the CB IL4 peptide conformation and cellular signaling functions using nuclear magnetic resonance spectroscopy, circular dichroism, G protein activation and cAMP production. Circular dichroism studies indicated that phosphorylation at various Ser residues induced helical structure in different environments.

Mouse Neuroblastoma CB Cannabinoid Receptor-Stimulated [S]GTPɣS Binding: Total and Antibody-Targeted Gα Protein-Specific Scintillation Proximity Assays.

G protein-coupled receptors (GPCRs) are important regulators of cellular signaling functions and therefore are a major target for drug discovery. The CB cannabinoid receptor is among the most highly expressed GPCRs in neurons, where it regulates many differentiated neuronal functions. One model system for studying the biochemistry of neuronal responses is the use of neuroblastoma cells originating from the C1300 tumor in the A/J mouse, including cloned cell lines NS20, N2A, N18TG2, N4TG1, and N1E-115, and various immortalized hybrids of neurons with N18TG2 cells.

Cannabinoid Receptor Interacting Protein 1a Competition with β-Arrestin for CB1 Receptor Binding Sites.

Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB receptor (CBR) distal C-terminal-associated protein that alters CBR interactions with G-proteins. We tested the hypothesis that CRIP1a is capable of also altering CBR interactions with β-arrestin proteins that interact with the CBR at the C-terminus. Coimmunoprecipitation studies indicated that CBR associates in complexes with either CRIP1a or β-arrestin, but CRIP1a and β-arrestin fail to coimmunoprecipitate with each other.

CB1 cannabinoid receptor-mediated increases in cyclic AMP accumulation are correlated with reduced Gi/o function.

Background: CB1 cannabinoid receptors (CB1Rs) stimulate Gi/o-dependent signaling pathways. CB1R-mediated cAMP increases were proposed to result from Gs activation, but CB1R-stimulated GTPγS binding to Gs has not heretofore been investigated.

Methods: Three models of CB1R-stimulated cAMP production were tested: pertussis toxin disruption of Gi/o in N18TG2 cells; L341A/A342L-CB1R expressed in Chinese hamster ovary (CHO) cells; and CB1 and D2 dopamine receptors endogenously co-expressed in MN9D cells.

Cannabinoid receptor interacting protein (CRIP1a) attenuates CB1R signaling in neuronal cells.

CB1 cannabinoid receptors (CB1R) are one of the most abundantly expressed G protein coupled receptors (GPCR) in the CNS and regulate diverse neuronal functions. The identification of GPCR interacting proteins has provided additional insight into the fine-tuning and regulation of numerous GPCRs. The cannabinoid receptor interacting protein 1a (CRIP1a) binds to the distal carboxy terminus of CB1R, and has been shown to alter CB1R-mediated neuronal function [1].

Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation.

Background And Purpose: Microglial cells are important mediators of the immune response in the CNS. The phytocannabinoid, cannabidiol (CBD), has been shown to have central anti-inflammatory properties, and the purpose of the present study was to investigate the effects of CBD and other phytocannabinoids on microglial phagocytosis.

Experimental Approach: Phagocytosis was assessed by measuring ingestion of fluorescently labelled latex beads by cultured microglial cells.

Amphetamine self-administration attenuates dopamine D2 autoreceptor function.

Dopamine D2 autoreceptors located on the midbrain dopaminergic neurons modulate dopamine (DA) neuron firing, DA release, and DA synthesis through a negative-feedback mechanism. Dysfunctional D2 autoreceptors following repeated drug exposure could lead to aberrant DA activity in the ventral tegmental area (VTA) and projection areas such as nucleus accumbens (NAcc), promoting drug-seeking and -taking behavior. Therefore, it is important to understand molecular mechanisms underlying drug-induced changes in D2 autoreceptors.

Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain.

Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord.