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PubMed1996

Formation of the mutagenic/carcinogenic imidazoquinoxaline-type heterocyclic amines through the unstable free radical Maillard intermediates and its inhibition by phenolic antioxidants.

Generation of the imidazoquinoxaline-type heterocyclic amines in the heated model system composed of glucose/glycine/creatinine in aqueous diethylene glycol was effectively prevented by phenolic antioxidants, butylated hydroxyanisole (BHA), propyl gallate (PG), sesamol, esculetin and epigallocatechin gallate (EGCG) in a dose-dependent manner. Generation of the mutagens in heated-and-dried bonito meat was effectively prevented on pretreatment with EGCG or green tea extract. Electron spin resonance (ESR) studies showed that the heated model mixture of glucose/glycine generated the unstable pyrazine cation radical, and its formation was inhibited by BHA, sesamol and EGCG. ESR-spin trapping studies using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and N-tert-butyl-alpha-phenylnitrone (PBN) showed that the heated model mixture of glucose/glycine or glucose/glycine/creatinine generated unstable carbon-centred radical(s), and their formation was effectively inhibited by BHA, sesamol and EGCG. It is likely that the unstable free radical Maillard intermediates played an important role in the formation of the imidazoquinoxaline-type heterocyclic amines, and the phenolic antioxidants effectively scavenged the radical species to prevent the mutagen formation.

Anticarcinogenic Agents↗

PubMed1998

Determination of volatile components in fresh, frozen, and freeze-dried Padrón-type peppers by gas chromatography-mass spectrometry using dynamic headspace sampling and microwave desorption.

"Padrón-type" peppers are a small variety of Capsicum annuum cultivated mainly in Galicia, Spain. To compare the effects of freezing and freeze-drying on the volatile components of Padrón-type peppers, preserved samples are analyzed by means of dynamic headspace sampling on an adsorbent followed by microwave desorption into a gas chromatograph equipped with a mass spectrometric detector. Sixty-five compounds are identified, including hydrocarbons, terpenes, alcohols, phenols, ethers, aldehydes, ketones, esters, pyrroles, pyrazines, and sulfurous compounds. Fresh whole, homogenized, and freeze-dried peppers have characteristic volatile-component profiles, whereas frozen peppers have a highly variable volatile-component profile.

Capsicum↗

PubMed1996

Naturally occurring diallyl disulfide inhibits the formation of carcinogenic heterocyclic aromatic amines in boiled pork juice.

Three heterocyclic aromatic amines, 2-amino-3-methyl-imidazo[4, 5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoxaline and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, have been found in boiled pork juice. We have investigated the effect of naturally occurring organosulfur compounds, which are present in garlic and onion, on mutagen formation in boiled pork juice. Six organosulfur compounds - diallyl disulfide (DAD), dipropyl disulfide (DPD), diallyl sulfide (DAS), allyl methyl sulfide (AMS), allyl mercaptan (AM) and cysteine - were added separately to the pork juice before reflux boiling and then the mutagenicity of each sample was examined with the Salmonella typhimurium strain TA98 in the presence of S9 mix. All six compounds were found to inhibit the mutagenicity of boiled pork juice. The greatest inhibitory effect was observed with DAD and DPD, and this was 111-fold higher than that of the lowest, cysteine. To elucidate the inhibitory effect of DAD on mutagen formation in boiled pork juice, the major mutagenic fractions were monitored after HPLC separation by their mutagenicity with S. typhimurium TA98. By comparing the retention times of authentic IQ compounds from boiled pork juice with those following the addition of DAD, we showed that the mutagenicity of three major fractions was significantly inhibited compared with those same fractions in boiled pork juice alone. In addition, the Maillard reaction products (MRPs) in the boiled pork juice with and without the addition of DAD were quantified and identified by capillary gas chromatography and gas chromatography-mass spectrometry. The results show that the reduction in the total amount of MRPs (pyridines, pyrazines, thiophenes and thiazoles) in boiled pork juice after boiling for 12 h is correlated with their mutagenicity. Among the MRPs, tetrahydrothiophene-3-one exhibited the strongest correlation. These data suggest that the inhibition of IQ mutagen formation by DAD is mediated through the reduction of MRPs production.

Allyl Compounds↗

PubMed1994

Characterization of the mutagen 2-amino-3-methylimidazo[4,5-f]quinoline prepared from a 2-methylpyridine/creatinine/acetylformaldehyde model system.

A mixture of 2-methylpyridine, creatinine and aldehydes was heated in diethylene glycol containing 5% water for 1 h at 140 degrees C. The mutagenic compounds were purified by XAD-2 column chromatography, acid/base partition, blue cotton treatment, thin layer chromatography and HPLC. The active substances purified from each step were monitored by their mutagenicity with Salmonella typhimurium TA98 in the presence of S9 mix. Among the mutagens collected, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was isolated from HPLC, and was identified by its UV and mass spectrum using a photodiode array detector and mass spectrometry. Our findings appear to be the first experimental evidence to substantiate the hypothetical pathway for the formation of IQ mutagens from a heated model system consisting of a pyridine or pyrazine derivative, an aldehyde and creatinine or creatine.

Biotransformation↗

PubMed1978

Resonance Raman spectra of riboflavin and its derivatives in the bound state with egg riboflavin binding proteins.

The resonance Raman spectra of riboflavin (RF) and its derivatives, including 3-deuterated (3-D RF), 3-methyl (3-CH3 RF), 3-carboxymethyl (3-CH2COOH RF), and 7,8-dichlororiboflavins (7,8-Cl RF), in H2O and D2O were observed in the 700-1700 cm-1 region. The fluorescence problem of riboflavin was overcome by complex formation of riboflavin with riboflavin binding proteins. The observed frequencies of Raman lines of RF are in good agreement with those of glucose oxidase obtained by Spiro et al. by the resonance CARS method, although the present spectral range is extended to much lower frequency with a higher signal-to-noise ratio than that for glucose oxidase. The observed Raman lines were assigned to the individual ring modes of isoalloxazine on the basis of the Raman spectra of appropriate model compounds such as uracil, pyrazine, and o-xylene. The 1253 cm-1 line of RF was shifted to ca. 1300 cm-1 for 3-D RF, 3-CH3 RF, and 3-CH2COOH RF, and accordingly can be assigned to the CN stretching mode of Ring III. The 1632 cm-1 line of RF was shifted for 7,8-Cl RF and was assigned to a Ring I mode. No Raman line mainly due to C = O stretching mode was observed in the present resonance Raman spectra.

Carrier Proteins↗

PubMed2005

Phenols, quinolines, indoles, benzene, and 2-cyclopenten-1-ones are oviductal toxicants in cigarette smoke.

Previously, we showed that pyridines and pyrazines in cigarette smoke inhibit oviductal functioning in vitro in nanomolar and picomolar doses. The purpose of this study was to determine the lowest observable adverse effect levels (LOAELs) of phenols, quinolines, indoles, benzene, and 2-cyclopenten-1-ones found in mainstream smoke solutions on ciliary beat frequency, oocyte pickup rate, and infundibular smooth muscle contraction using the hamster oviduct. After solid phase extraction, mainstream smoke solution fractions were tested in the oviductal assays. The active fractions were analyzed using gas chromatography-mass spectrometry to identify individual chemicals. Using this approach, benzene, eleven phenolic, two indole, two quinoline, and two 2-cyclopenten-1-one derivatives were identified in the active fractions. Commercially available authentic standards of the identified compounds were tested in dose-response studies on hamster oviducts. The LOAELs were determined for each compound using the ciliary beat frequency, oocyte pickup rate, and infundibular smooth muscle contraction rate assays. Indole, the compound with the highest potency, showed inhibition of ciliary beat frequency (10(-13) M), oocyte pickup rate (10(-14) M), and infundibular smooth muscle contraction rate (10(-15) M) in femtomolar doses. All of the other compounds tested, except phenol, which only showed inhibition at millimolar concentrations, were inhibitory in picomolar, nanomolar, or micromolar concentrations. Derivitization of phenol increased its toxicity in the oviductal assays, especially when a methyl or ethyl group was substituted on the fourth position. The indoles, quinolines, and four phenolic compounds had both high potencies and efficacies in the oviductal assays.

Animals↗

PubMed2003

Extended quantum critical phase in a magnetized spin-1/2 antiferromagnetic chain.

Measurements are reported of the magnetic field dependence of excitations in the quantum critical state of the spin S=1/2 linear chain Heisenberg antiferromagnet copper pyrazine dinitrate (CuPzN). The complete spectrum was measured at k(B)T/J< or =0.025 for H=0 and H=8.7 T, where the system is approximately 30% magnetized. At H=0, the results are in agreement with exact calculations of the dynamic spin correlation function for a two-spinon continuum. At H=8.7 T, there are multiple overlapping continua with incommensurate soft modes. The boundaries of these continua confirm long-standing predictions, and the intensities are consistent with exact diagonalization and Bethe ansatz calculations.

Journal Article↗

PubMed2004

Optimal control approach to suppression of radiationless transitions.

We propose a general approach for eliminating radiationless transitions in polyatomic molecules and illustrate it through the example of the S2-->S1 internal conversion of pyrazine. Essential to our approach is the phenomenon of electronically localized eigenstates of strongly vibronically coupled Hamiltonians. The occurrence of such states, observed here for the first time, and its generality are traced to the origin of scars of periodic orbits.

Journal Article↗

PubMed2005

First principles calculations of mechanical properties of 4,4'-bipyridine attached to Au nanowires.

A first attempt is made to calculate the forces involved in the breaking of nanowires consisting of a molecule attached to nanosized metallic pieces. As a model system, we consider different Au nanowires connected by a 4,4(')-bipyridine or pyrazine molecule, for which density functional calculations were performed at different elongations. The geometry of the system was optimized for different forces applied. In all cases the calculated maximum forces were close to 1 nN, which is of the order of the experimental values, and smaller than the corresponding to the rupture of the Au-Au chain (1.5-1.6 nN). When 4,4(')-bipyridine is attached to Au monoatomic nanowire, the maximum force required to break the Au-Au bond may be lowered to values close to that obtain to break the Au-N bond, but when 4,4(')-bipyridine is attached to small Au clusters, the breaking of the nanowire takes place at the Au-N bond only.

Journal Article↗

PubMed2002

Some errors from the crystallographic literature, some amplifications and a questionable result.

The space groups of [[Mo(2)(O(2)CCH(3))(4)('linker')](n)] are corrected from P1 to C2/m for 'linker' = pyrazine and 1,4-diazabicyclo[2.2.2]octane (dabco) and from P1 to C2/c for 'linker' = 4,4'-bipyridine. Also, [[tris-(2-pyridylmethyl)amine]BrV(mu-O)VBr[tris-(2-pyridylmethyl)amine]]Br.H(2)O is corrected from P1 to C2/c. These Laue class changes allow more reliable crystallochemical comparisons to be made among families of related structures. Space groups are corrected for 4-methyl-2,6-bis(4-methylbenzylidene)cyclohexanone, 2,6-bis(4-dimethylaminobenzylidene)cyclohexanone, K[Cr(tetramethylenediamine-N,N,N',N'-tetraacetate)].H(2)O and [bis(11,-11-dimethyl-3,4:8,9-dibenzobicyclo[4.4.1]undeca-3,8-diene)-(tetracyanoethylene)]. The conflicting reports for Cu(H(2)O)-(phenanthroline)(2)(X)(2), where X = ClO(4), NO(3) and BF(4), are resolved. Three related examples of open framework host-guest structures with space groups 'Cc or C2/c' are discussed. Adding centers to 2,2'-bi-1H-imidazolium dipicrate and [tris(2,2'-bi-1H-imidazole)bis[2-(2-1H-imidazolyl)-1H-imidazolium]bis(iodide)] corrects discrepancies of up to 0.38 A between chemically similar hydrogen-bond distances. Wrongly identified atoms are corrected in theta-[bis(ethylenedithio)tetrathiafulvalene](2) (CsCd)(SCN)(4) and (purported) diaquadihydroxotetrakis(m-nitrobenzenesulfonate)discandium(III). The reported difference between the crystal structure of (CH(3)NH(3))(4)YbCl(7) and those of the other members of this family of (CH(3)NH(3))(4)MX(7) (M = In, Fe, V; X = Cl, Br) structures is pointed out in the context of possibly different N-H...Cl hydrogen bonding in the Yb structure.

Journal Article↗

PubMed1995

Structure-function relations in the inhibition of murine contact hypersensitivity by amiloride.

Topical application of amiloride, a potent inhibitor of the Na+/H+ antiport, inhibits cutaneous inflammation induced by ultraviolet radiation or contact hypersensitivity in mice. Amiloride analogues with greater and lesser inhibition of the Na+/H+ exchange were tested to determine whether anti-inflammatory effects correlate with this activity. Structural analogues of amiloride without significant activity at the Na+/H+ antiport (pyrazine, pyrazinamide, and chloropyrazine) failed to inhibit contact hypersensitivity. N-amidino-3-amino-5-dimethyl amino-6-chloropyrazinecarboxamide (DMA) has a 23-fold greater affinity for the Na+/H+ antiport compared to amiloride, but failed to inhibit contact hypersensitivity in this assay. 3,5-diamino-6-chloropyrazine-amido-guanidine (DCG), which has only 7% of the affinity of amiloride for the antiport, suppressed contact hypersensitivity as well as amiloride. Experiments examining the ability of these agents to diffuse through mouse skin revealed amiloride to be superior to both DCG and DMA, which were approximately equal. DMA, with greater inhibition of the Na+/H+ antiport but lesser ability to inhibit contact hypersensitivity, inhibited protein synthesis and induced cell death more than amiloride or DCG. Amiloride and DCG hold promise as topical anti-inflammatory agents. Their anti-inflammatory properties do not correlate with affinity for the Na+/H+ antiport, ability to penetrate murine skin, or inhibition of protein synthesis.

Amiloride↗

PubMed2005

Volatile compounds of Soumbala, a fermented African locust bean (Parkia biglobosa) food condiment.

AIMS: To determine the profile of volatile compounds responsible for the aroma of Soumbala produced spontaneously and with pure and mixed cultures of Bacillus subtilis and Bacillus pumilus. METHODS AND RESULTS: Traditional and controlled fermentation trials of African locust bean with pure and mixed starter cultures of B. subtilis (B7, B9 and B15) and B. pumilus (B10) were performed. Aroma volatiles were analysed using Likens-Nikerson method coupled with gas chromatography and mass spectrophotometry. Sensory analysis of Soumbala as well as rice dishes prepared with each type of Soumbala were carried out by 10 panellists. In total 116 compounds were identified. They included pyrazines, aldehydes, ketones, esters, alcohols, acids, alkanes, alkenes, amines, pyridines, benzenes, phenols, sulphurs, furans and other compounds. Using principal component analysis for comparison, the aroma profiles of the Soumbala samples could be separated into three groups. The sensory evaluation showed variable acceptability. However, it was noticed that Soumbala samples produced with starter cultures were scored higher than traditionally prepared Soumbala. CONCLUSIONS: Aroma volatiles and organoleptic properties of Soumbala vary according to the Bacillus isolates involved in the fermentation. SIGNIFICANCE AND IMPACT OF THE STUDY: This study contributes to the selection of Bacillus starter cultures for controlled production of Soumbala.

Bacillus↗

PubMed1981

On the molecular and submolecular structure of the semiquinone cations of alloxazines and isoalloxazines as revealed by electron-paramagnetic-resonance spectroscopy.

The thermodynamically stable and, therefore, analytically most important alloxazine and isoalloxazine radical cations have been studied in detail by electron paramagnetic resonance (EPR) spectroscopy. Isotopic and chemical substitutions have been made as in earlier studies with the less stable neutral and anionic species. The experimental spectra have been calculated with the aid of a more sophisticated computer-simulation program than previously used. Excellent fits were obtained only when all of the following atoms were taken into account in the hyperfine coupling scheme: N-5 H, N-10 H or CH3, C-6 H, C-7 H, C-8 H or CH3 and C-9 H. An additional but small coupling constant was required for the fit. This latter coupling constant is assigned to the nitrogen atom(s) of the pyrimidine subnucleus of (iso)alloxazine radical cations. The EPR-active proton is attached to N-5 as we also found for the neutral flavosemiquinone. The alloxazine and isoalloxazine radical cations exhibit an identical hyperfine coupling scheme but differ especially in the pyrazine nucleus with respect to the spin density distribution. This suggests that the geometrical structure of the two kinds of radicals is somewhat different. The highest spin density is, however, located at N-5 of (iso)alloxazine as has been found for the other flavosemiquinone species. The hyperfine coupling constants are interpreted in terms of spin densities and comparison is made with the most recently available quantum chemical calculations. All monomeric flavosemiquinone species are compared with each other and their differences in the submolecular structure are discussed briefly.

Benzoquinones↗

PubMed1983

Chemical-modification studies on rat olfactory mucosa using a thiol-specific reagent and enzymatic iodination.

1. A rat olfactory preparation, suitable for biochemical studies in vitro on olfactory mechanisms, is described. 2. The effects of the impermeant chemical modification reagents mersalyl (a thiol reagent) and enzymatic iodination, on the amplitude of the electroolfactogram (EOG) responses elicited from rat olfactory mucosa by pulses of odorant vapours was studied using 12 odorants differing widely in odour quality and molecular structure: amyl acetate, carvone, decanal, butylamine, cineole, citronellol, cresol, diacetyl, dimethylethyl-pyrazine, naphthalene, octanethiol and valeric acid. 3. Both reagents irreversibly reduced the EOG amplitude to all odorants to an extent dependent on the reagent concentration. Two subpopulations of animal preparations could be distinguished on the basis of the extent to which they survived the iodination whereas mersalyl appeared to sample a single population of preparations. 4. Small but statistically significant differences were observed between the responses of each odorant with each reagent but no simple correlation between either the molecular structure or odour quality of the odorants and the reagent effect is apparent for the case of mersalyl. With iodination the responses from the three flexible-aliphatic-chain odorants were reduced to a greater extent than the other odorants, all of which had a dissimilar molecular structure. 5. The ability of three odorants, amyl acetate, carvone and decanal, to protect the receptors for the odorants against chemical modification was investigated. The protecting odorants were applied directly to the mucosa as a dilute solution in Ringer's medium. No specific odorant protection effects were observed. 6. The results are discussed in relation to a model of the olfactory mechanism involving relatively non-specific receptor proteins. Each receptor type is envisaged as interacting weakly with a number of odorants and each odorant interacts with a number of receptors.

Aldehydes↗

PubMed1985

Nuclear magnetic resonance studies of the old yellow enzyme. 2. 13C NMR of the enzyme recombined with 13C-labeled flavin mononucleotides.

The apoenzyme of NADPH oxidoreductase, 'old yellow enzyme', was reconstituted with selectively 13C-enriched flavin mononucleotides and investigated by 13C NMR spectroscopy. The 13C NMR results confirm the results obtained by 15N NMR spectroscopy and yield additional information about the coenzyme-apoenzyme interaction. A strong deshielding of the C(2) and C(4) atoms of enzyme-bound FMN both in the oxidized and reduced state is observed, which is supposed to be induced by hydrogen-bond formation between the protein and the two carbonyl groups at C(2) and C(4) of the isoalloxazine ring system. The chemical shifts of all 13C resonances of the flavin in the two-electron-reduced state indicate that the N(5) atom is sp3-hybridized. From 31P NMR measurements it is concluded that the FMN phosphate group is not accessible to bulk solvent. The unusual 31P chemical shift of FMN in old yellow enzyme seems to indicate a different binding mode of the FMN phosphate group in this enzyme as compared to the flavodoxins. The 13C and 15N NMR data on the old-yellow-enzyme--phenolate complexes show that the atoms of the phenolate are more deshielded whereas the atoms of the enzyme-bound isoalloxazine ring are more shielded upon complexation. A non-linear correlation exists between the chemical shifts of the N(5) and the N(10) atoms and the pKa value of the phenolate derivative bound to the protein. Since the chemical shifts of N(5), N(10) and C(4a) are influenced most on complexation it is suggested that the phenolate is bound near the pyrazine ring of the isoalloxazine system. 15N NMR studies on the complex between FMN and 2-aminobenzoic acid indicate that the structure of this complex differs from that of the old-yellow-enzyme--phenolate complexes.

Apoenzymes↗

PubMed1990

A two-dimensional 1H-NMR study on Megasphaera elsdenii flavodoxin in the oxidized state and some comparisons with the two-electron-reduced state.

Assignments for the 137 amino acid residues of oxidized Megasphaera elsdenii flavodoxin have been made using the sequential resonance assignment procedure. Great benefit was experienced from assignments of the fully reduced protein. The secondary and tertiary structures of the typical alpha/beta protein remain virtually identical on going from the oxidized to the two-electron-reduced state as judged from two-dimensional NOE spectroscopy. However, functionally important conformation changes in the flavin-binding region do occur on reduction. Considerable reduction-state-dependent chemical shift variations of protons in the immediate vicinity of the isoalloxazine moiety take place. From analysis of these shifts, it can be concluded that ring current effects of the pyrazine part of the flavin diminish on two-electron reduction.

Amino Acid Sequence↗

PubMed2005

Activation of NADPH oxidase and extracellular superoxide production in seizure-induced hippocampal damage.

We sought to determine whether the extracellular compartment contributed to seizure-induced superoxide (O2*-) production and to determine the role of the NADPH oxidase complex as a source of this O2*- production. The translocation of NADPH oxidase subunits (p47phox, p67phox and rac1) was assessed by immunoblot analysis and NADPH-driven O2*- production was measured using 2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)-8-benzyl-3,7-dihydroimidazo [1,2-alpha] pyrazin-3-one-enhanced chemiluminescence. Kainate-induced status epilepticus resulted in a time-dependent translocation of NADPH oxidase subunits (p47phox, p67phox and rac-1) from hippocampal cytosol to membrane fractions. Hippocampal membrane fractions from kainate-injected rats showed increased NADPH-driven and diphenylene iodonium-sensitive O2*- production in comparison to vehicle-treated rats. The time-course of kainate-induced NADPH oxidase activation coincided with microglial activation in the rat hippocampus. Finally, kainate-induced neuronal damage and membrane oxygen consumption were inhibited in mice overexpressing extracellular superoxide dismutase. These results suggest that seizure activity activates the membrane NADPH oxidase complex resulting in increased formation of O2*-.

Animals↗

PubMed2006

Pharmacological characterization of 5-hydroxytryptamine-induced contraction in the chicken gastrointestinal tract.

5-Hydroxytryptamine (5-HT) receptor subtypes involved in 5-HT-induced contraction of the chicken gastrointestinal tract were characterized pharmacologically using subtype-selective agonists and antagonists. The proventriculus (area of stomach adjacent to the oesophagus) and ileum are examined. 5-HT applied cumulatively caused sustained contraction of the proventriculus that was not decreased by tetrodotoxin, atropine or l-nitro-arginine methylester (l-NAME). alpha-Methyl-5-HT showed the same potency as that of 5-HT, indicating the involvement of the 5-HT(2) receptor. (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane (DOI), 5-methoxytryptamine and 1-(3-chlorophenyl)piperazine hydrochloride (mCPP) were potent, and 2-methyl-5-HT, 5-carboxamidotryptamine, BW723C86 and 6-chloro-2-(1-piperazinyl)pyrazine hydrochloride (MK212) were moderate, but (+/-)-8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT), [endo-N-8-methyl-8-azabicyclo-(3,2,1)oct-3-yl]-2,3-dihydro-(1-methyl)ethyl-2-oxo-1H-benzimidazol-1-carboxamide (BIMU-8) and cisapride were weak agonists. Correlation of pEC(50) values of these agonists with documented pEC(50) values for 5-HT(2C) receptor was higher than 5-HT(2A) and 5-HT(2B). Cinanserin, ketanserin, methiothepin, methysergide, mianserin, (8-[5-(2,4-dimethoxy-5-(4-trifluoromethylphenylsulphonamido)phenyl-5-oxopentyl)-1,3,8-triazaspiro[4,5]decane-2,4-dione hydrochloride (RS102221), N-(1-methyl-1H-indolyl-5-yl)-N'-(3-methyl-5-isothiazolyl)urea (SB204741), spiperone and N-desmethylclozapine concentration-dependently inhibited the contractile responses to 5-HT. Correlation of pK(b)/pA(2) of antagonists with documented pK(i) for 5-HT(2C) receptor was highest among 5-HT(2) receptor subtypes. In the methysergide- and ketanserin-treated proventriculus, 5-HT, 2-methyl-5-HT and cisapride did not enhance the electrical field stimulation (5 Hz)-induced cholinergic contractions. 5-HT applied non-cumulatively caused transient contraction of ileum, and the responses were partly decreased by atropine or tetrodotoxin. 5-Methoxytryptamine, alpha-methyl-5-HT, 5-carboxamidotryptamine, L692,247 and DOI were potent agonists. However, 2-methyl-5-HT, cisapride, BW723C86, 8-OH-DPAT and 5-nonyloxytryptamine, mCPP and MK212 were less effective. Ketanserin and methysergide decreased the 5-HT-induced ileal contraction, but neither GR113808 nor SB269970 inhibited the responses. In conclusion, 5-HT causes contraction of the proventriculus via 5-HT(2C)-like receptors present on smooth muscle. 5-HT also causes contraction of the ileum, but the underlying mechanisms are complex, involving neural and smooth muscle components, and both 5-HT(1)- and 5-HT(2)-like receptors. Neural 5-HT receptors similar to 5-HT(3)/5-HT(4) receptors were not found in the chicken proventriculus and ileum.

Anesthetics, Local↗