Nicotine-induced catecholamine (CA) secretion and inward ionic currents were inhibited by the opioid antagonist naloxone in cultured bovine chromaffin cells. Naloxone inhibited nicotine-induced CA secretion, as detected by an on-line real-time electrochemical technique, in a dose-dependent manner (IC(50)=29 microM). In voltage-clamped chromaffin cells, nicotine (10 microM) evoked an average pea...

BACKGROUND Pterodon pubescens Benth seeds are commercially available in the Brazilian medicinal plant street market. The crude alcoholic extracts of this plant are used in folk medicine as anti-inflammatory, analgesic, and anti-rheumatic preparations. The aim of this study was to evaluate the contribution of geranylgeraniol (C1) and 6alpha, 7beta-dihydroxyvouacapan-17beta-oate methyl ester (C2)...

Drugs targeting G-protein-coupled receptors (GPCRs) make up more than 25% of all prescribed medicines. The ability of GPCRs to form heteromers with unique signaling properties suggests an entirely new and unexplored pool of drug targets. However, current in vitro assays are ill equipped to detect heteromer-selective compounds. We have successfully adapted an approach, using fusion proteins of G...

The synthesis and the effect of a combination of 6-glycine and 14-phenylpropoxy substitutions in N-methyl- and N-cycloproplymethylmorphinans on biological activities are described. Binding studies revealed that all new 14-phenylpropoxymorphinans (11-18) displayed high affinity to opioid receptors. Replacement of the 14-methoxy group with a phenylpropoxy group led to an enhancement in affinity t...

Salvinorin A is a pharmacologically active diterpene that occurs naturally in the Mexican mint Ska Maria Pastora (Salvia divinorum) and represents the first naturally occurring kappa-opioid receptor agonist. The chemical structure of salvinorin A is novel among the opioids, and thus defines a new structural class of kappa-opioid-receptor selective drugs. Few studies have examined the effects of...

The pharmacological profile of opioid-binding sites in zebrafish brain homogenates has been studied using radiolabeled binding techniques. The nonselective antagonist [(3)H]diprenorphine binds with high affinity (K(D) = 0.27 +/- 0.08 nM and a B(max) = 212 +/- 14.3 fmol/mg protein), displaying two different binding sites with affinities of K(D1) = 0.08 +/- 0.02 nM and K(D2) = 17.8 +/- 9.18 nM. T...

The well characterized human breast cancer cell line, MCF-7, has been shown to possess membrane receptors for various opioid ligands, and these compounds have been shown to modulate the growth of the cells in culture. Using specific radioligands for the receptor types, we were able to demonstrate that the MCK-7 cells possess multiple opioid receptor types. Relatively high-affinity-binding sites...

Classically, pain sensation or suppression has been attributed exclusively to neuronal circuits. This review challenges this notion and presents an expanded concept about the contribution of immune mechanisms in the inhibition of pain (analgesia). Among the many transmitters with potential for neuroimmune interactions, we concentrate here on opioids, the most extensively investigated compounds....