溴氰菊酯中毒引起家蝇神经系统环腺苷酸(cAMP)含量的改变

环腺苷酸(cAMP)可在神经传递物刺激腺苷酸环化酶的作用下产生,而坏腺苷酸又可促成神经传递物的产生.用溴氰菊酯(deltamethrin)处理家蝇后,发现酪胺大量增加,主要由于酪氨酸脱羧酶受到诱导、活性增高所致.处理后一小时,cAMP也有增加,并与酶活性的增加相平行,但酪氨酸脱羧酶活性增高的曲线与cAMP量增加的曲线,实际上并不平行,因酪氨酸脱羧酶的活性是先增加,然后下降,而cAMP的量则是在开始时有一个小的下降,接着一直上升,而此时酶的诱导已下降,cAMP含量在诱导开始时出现下降的原因尚不明,可能与环鸟苷酸(cGMP)有关.但随后的上升显然是由于酪胺或章鱼胺的增加所造成.目前已证实,酪胺可经β-羟化作用形成章鱼胺,后者再刺激章鱼胺受体,而使腺苷酸环化酶活化,产生大量的cAMP.酪胺本身也可能就是章鱼胺受体的激活剂.     

Phénolamides et induction florale de Cichorium intybus dans différentes conditions de culture en serre ou in vitro

Phenolamides and floral induction of Cichorium intybus in different conditions of culture in glass-room or in vitro. Three complexes between phenols and amines (phenolamides) have been found in Cichorium intybus L., a plant with an absolute requirement of vernalisation followed by long days for flowering. Upon hydrolysis, these complexes (A, B and C) liberate aromatic amines whose exact identification is in progress, but which are closely related to dopamine, tyramine and serotonin, respectively. In a first series of experiments, phenolamides were studied in the buds of plants grown in the greenhouse under varying conditions. Only buds from plants which flower in long days contained large amounts of these compounds. Much smaller amounts were found in buds at the end of vernalisation (at 2–4°C) before long-day treatment as well as in buds kept in the vegetative state after vernalisation by being grown in short days (8 h light) or in total darkness. In a second series of experiments, phenolamides were studied in bud-forming calli induced in vitro on explants of tuberised root. After sixteen days of culture in continuous light, large quantities of phenolamide were found in the buds and calli of the upper part of the explant, while the lower part which never produces buds contained much less. Buds formed under continuous light produce inflorescences in approximately one month. Various other culture conditions make it possible to maintain the explants in the vegetative state. This can be obtained by short-day conditions, or otherwise under continuous illumination by decreasing the sugar or increasing the NAA levels in the medium. After 13 days of culture, the phenolamide levels were much lower under all of these conditions, than under conditions favourable to floral induction. Compound C is absent or present in trace amounts in vegetative buds. The significance of the differences observed between floral and vegetative buds is supported by the sensitivity of the analytical techniques used. The accumulation of phenolamides in tissues of Cichorium intybus appears to be closely linked to floral induction. Under continuous light it begins very early in young buds and even in the calli that bear these buds.     

Trace amines and Tourette's syndrome

There has been considerable interest in recent years in possible neurochemical abnormalities in Tourette's Syndrome (TS). In studies combining neuropsychological and neurochemical measurements, we have investigated the possible roles of trace amines in this disorder. Urinary levels of free -phenylethylamine (PEA) and plasma levels of its precursor amino acid phenylalanine were decreased in TS patients when compared to values in normal children. These urinary PEA levels in TS patients were inversely related to several scores from the Tourette's Syndrome Global Scale (TSGS). Further investigation of the group of subjects with low urinary PEA indicated that they also had low levels of MHPG, normetanephrine, 5-HT andm- andp-tyramine. Patients with low PEA were also compared on an extensive battery of neuropsychological measures and observed to perform significantly worse than TS patients with normal urinary PEA levels. Biochemical measurements also suggest a possible abnormality in tryptamine turnover in TS since urinary levels of indole-3-acetic acid (IAA; the acid metabolite of tryptamine) are significantly lower in TS patients than in normal controls.     

A new biologically active phenolic from Cattleya trianaei

A new phenolic, hydroxyeucomic acid, and dopamine were isolated from Cattleya trianaei and their biological activities examined.     

Ultrasonic synthesis of tyramine derivatives as novel inhibitors of α-glucosidase in vitro

Tyramine derivatives 3–27 were synthesized by using conventional and environmental friendly ultrasonic techniques. These derivatives were then evaluated for the first time for their α-glucosidase (Sources: Saccharomyces cerevisiae and mammalian rat-intestinal acetone powder) inhibitory activity by using in vitro mechanism-based biochemical assays. Compounds 7, 14, 20, 21 and 26 were found to be more active (IC₅₀?=?49.7?±?0.4, 318.8?±?3.7, 23.5?±?0.9, 302.0?±?7.3 and 230.7?±?4.0?μM, respectively) than the standard drug, acarbose (IC₅₀?=?840.0?±?1.73?μM (observed) and 780?±?0.028?μM (reported)) against α-glucosidase obtained from Saccharomyces cerevisiae. Kinetic studies were carried out on the most active members of the series in order to determine their mode of inhibition and dissociation constants. Compounds 7, 20 and 26 were found to be the competitive inhibitors of α-glucosidase. These compounds were also screened for their protein antiglycation, and dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. Only compounds 20, 22 and 27 showed weak antiglycation activity with IC₅₀ values 505.27?±?5.95, 581.87?±?5.50 and 440.58?±?2.74?μM, respectively. All the compounds were found to be inactive against DDP-IV enzyme. Inhibition of α-glucosidase, DPP-IV enzymes and glycation of proteins are valid targets for the discovery of antidiabetic drugs. Cytotoxicity of compounds 3–27 was also evaluated by using mouse fibroblast 3T3 cell lines. All the compounds were found to be noncytotoxic. The current study describes the synthesis α-glucosidase inhibitory activity of derivatives, based on a natural product tyramine template. The compounds reported here may serve as the starting point for the design and development of novel α-glucosidase inhibitors as antidiabetic agents.     

Substituent-dependent, positive and negative modulation of Bombyx mori adenylate cyclase by synthetic octopamine/tyramine analogues

Octopamine (OCT)/tyramine (TYR) analogues, mainly including p- and beta-substituted phenylethylamines, were prepared as probes for the ligand-binding site(s) of adenylate cyclase-coupled OCT or TYR receptors, and were examined for their effects on cAMP production in the head membranes of Bombyx mori larvae. Small structural changes in OCT and TYR proved to lead to three types of OCT/TYR analogues: (1) compounds that increase the cAMP level by themselves and also depress OCT-stimulated cAMP production, (2) compounds that do not stimulate cAMP production by themselves but inhibit OCT-stimulated cAMP production, and (3) compounds that are not active in either the stimulation of cAMP production or the inhibition of OCT-stimulated cAMP production. Tyramine, which belongs to the second group, also inhibited the basal level of cAMP production at high concentrations. The data indicate that two biogenic amine systems that positively and negatively regulate the level of the second messenger cAMP are present in the head part of B. mori larvae. This finding points to the necessity of separately evaluating the positive and negative regulatory effects in order to quantitatively understand the structure-activity relationships of OCT receptor ligands. Arch.     

Positive and negative modulation of Bombyx mori adenylate cyclase by 5-phenyloxazoles: identification of octopamine and tyramine receptor agonists

Nineteen 5-phenyloxazoles (5POs) were examined for their ability to modulate adenylate cyclase by measuring cAMP produced in head membrane homogenates of fifth instar larvae of the silkworm Bombyx mori. Among the compounds tested, 5-(4-methoxyphenyl)oxazole (9) and the 2,6-dichlorophenyl congener showed the highest activation of adenylate cyclase; both compounds produced approximately half the level of cAMP produced by the action of octopamine (OCT). The OCT receptor antagonists chlorpromazine, mianserin, and metoclopramide attenuated 9-stimulated cAMP production. In contrast, 5-(4-hydroxyphenyl)oxazole (8) and the 4-cyanophenyl congener attenuated both OCT-stimulated and basal cAMP production. The tyramine (TYR) receptor antagonist yohimbine inhibited the negative effect of 8. These findings indicate that the 5PO class of compounds includes both positive and negative modulators of adenylate cyclase in the heads of B. mori larvae, and that 9 and 8 are OCT and TYR receptor agonists, respectively. These compounds might prove useful for a pharmacological dissection of biogenic amine receptors.     

Plasma bikunin: Half-life and tissue uptake

Bikunin is a chondroitin sulfate-containing plasma protein synthesized in the liver. In vitro, it has been shown to inhibit proteases and to have additional activities, but its biological function is still unclear. Here we have studied the dynamics of plasma bikunin in rats and mice. A half-life of 7 ± 2 min was obtained from the time course of the decrease of the plasma level of bikunin following hepatectomy. Clearance experiments with intravenously injected radiolabeled bikunin with or without the chondroitin sulfate chain showed that the polysaccharide had little influence on the elimination rate of the protein. The uptake of bikunin by different tissues was studied using bikunin labeled with the residualizing agent ¹²⁵I-tyramine cellobiose; 60 min after intravenous injection, 49% of the radioactivity was recovered in the kidneys and 6–11% in the liver, bones, skin, intestine and skeletal muscle. The uptake in the liver was analyzed by intravenous injection of radiolabeled bikunin followed by collagenase perfusion and dispersion of the liver cells. These experiments indicated that bikunin is first trapped extracellularly within the liver before being internalized by the cells. (Mol Cell Biochem 271: 61–67, 2005)     

TYRA-2 (F01E11.5): a Caenorhabditis elegans tyramine receptor expressed in the MC and NSM pharyngeal neurons

Tyramine appears to regulate key processes in nematodes, such as pharyngeal pumping, and more complex behaviors, such as foraging. Recently, a Caenorhabditis elegans tyramine receptor, SER-2, was identified that is involved in the TA-dependent regulation of these processes. In the present study, we have identified a second C. elegans gene, tyra-2 (F01E11.5) that encodes a tyramine receptor. This is the first identification of multiple tyramine receptor genes in any invertebrate. Membranes from COS-7 cells expressing TYRA-2 bind [(3)H]tyramine with high affinity with a K(d) of 20 +/- 5 nM. Other physiologically relevant biogenic amines, such as octopamine and dopamine, inhibit [(3)H]tyramine binding with much lower affinity (K(i)s of 1.55 +/- 0.5 and 1.78 +/- 0.6 microM, respectively), supporting the identification of TYRA-2 as a tyramine receptor. Indeed, tyramine also dramatically increases GTPgammaS binding to membranes from cells expressing TYRA-2 (EC(50) of 50 +/- 13 nM) and the TA-dependent GTPgammaS binding is PTX-sensitive suggesting that TYRA-2 may couple to Galpha(i/o). Based on fluorescence from tyra::gfp fusion constructs, TYRA-2 expression appears to be exclusively neuronal in the MC and NSM pharyngeal neurons, the AS family of amphid neurons and neurons in the nerve ring, body and tail. Taken together, these results suggest that TYRA-2 encodes a second Galpha(i/o)-coupled tyramine receptor and suggests that TA-dependent neuromodulation may be mediated by multiple receptors and more complex than previously appreciated.