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Biomedical subjects

M Petersen

Publications and source records attributed to M Petersen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Induction of bile ducts in embryonic liver by mesenchyme: a new perspective for the treatment of biliary atresia?

Presently only those forms of Extrahepatic Biliary Atresia (EHBA) with minimal or no intrahepatic manifestations can be treated successfully by extensive hepatoportoenterostomy. Intraoperative macro- and microscopic observations show that the typical pathogenetic manifestations in EHBA are most prominent at the porta hepatis. We therefore postulate that EHBA is the result of a defective embryonic development of the porta hepatis. In rat embryos hepatic bile duct formation is initiated at the porta hepatis and in this context mesenchyme from the periportal region seems to play a major inductive role. In order to demonstrate the role of invading periportal mesenchyme for the process of bile duct rudiment formation we established an organ culture model of the embryonic porta hepatis by recombining periportal mesenchyme with peripheral liver fragments from 15 days old rat embryos (Carnegie Stage 21). The degree of mesenchyme invasion as well as the formation of mesenchyme-surrounded liver cell clusters, rosettes or vesicles (bile duct rudiments) were assessed. Mesenchyme from the porta hepatis invaded the peripheral liver fragments and induced the formation of mesenchyme-surrounded liver cell clusters and rosettes with the beginning of lumen formation. Kidney mesenchyme recombined with liver fragments as a mesenchymal alternative showed almost the same effect, lung mesenchyme showed only a very weak inductive effect. To assess the effect of a diffusible factor versus direct cell contact, a millipore filter with and without paraffin coating was interposed between mesenchyme containing tissue and peripheral liver tissue fragments. Without direct cell contact to mesenchyme no hepatoblast cluster or rosette formation could be observed. Comparing this result to the normal development of the liver in rats our investigations suggest that the embryogenesis of the porta hepatis is probably defined by the following two developmental steps: First, differentiation of the intrahepatic bile duct system which is induced by invading mesenchyme originating from the extrahepatic periportal region and realized by epithelium mesenchyme interaction. Second, fusion of extra- and intrahepatic bile duct systems at the level of the later porta hepatis. Disturbances of this complex process can possibly lead to biliary atresia. Further investigations regarding details of the role of the mesenchyme, its inductive factors and the kidney mesenchyme's inductive potential in liver development may provide a new perspective for future treatment of biliary atresia.

Animals↗
PubMed2001

Erosion of root epidermal cell walls by Rhizobium polysaccharide-degrading enzymes as related to primary host infection in the Rhizobium-legume symbiosis.

A central event of the infection process in the Rhizobium-legume symbiosis is the modification of the host cell wall barrier to form a portal of entry large enough for bacterial penetration. Transmission electron microscopy (TEM) indicates that rhizobia enter the legume root hair through a completely eroded hole that is slightly larger than the bacterial cell and is presumably created by localized enzymatic hydrolysis of the host cell wall. In this study, we have used microscopy and enzymology to further clarify how rhizobia modify root epidermal cell walls to shed new light on the mechanism of primary host infection in the Rhizobium-legume symbiosis. Quantitative scanning electron microscopy indicated that the incidence of highly localized, partially eroded pits on legume root epidermal walls that follow the contour of the rhizobial cell was higher in host than in nonhost legume combinations, was inhibited by high nitrate supply, and was not induced by immobilized wild-type chitolipooligosaccharide Nod factors reversibly adsorbed to latex beads. TEM examination of these partially eroded, epidermal pits indicated that the amorphous, noncrystalline portions of the wall were disrupted, whereas the crystalline portions remained ultrastructurally intact. Further studies using phase-contrast and polarized light microscopy indicated that (i) the structural integrity of clover root hair walls is dependent on wall polymers that are valid substrates for cell-bound polysaccharide-degrading enzymes from rhizobia, (ii) the major site where these rhizobial enzymes can completely erode the root hair wall is highly localized at the isotropic, noncrystalline apex of the root hair tip, and (iii) the degradability of clover root hair walls by rhizobial polysaccharide-degrading enzymes is enhanced by modifications induced during growth in the presence of chitolipooligosaccharide Nod factors from wild-type clover rhizobia. The results suggest a complementary role of rhizobial cell-bound glycanases and chitolipooligosaccharides in creating the localized portals of entry for successful primary host infection.

Cell Wall↗
PubMed2000

Arabidopsis map kinase 4 negatively regulates systemic acquired resistance.

Transposon inactivation of Arabidopsis MAP kinase 4 produced the mpk4 mutant exhibiting constitutive systemic acquired resistance (SAR) including elevated salicylic acid (SA) levels, increased resistance to virulent pathogens, and constitutive pathogenesis-related gene expression shown by Northern and microarray hybridizations. MPK4 kinase activity is required to repress SAR, as an inactive MPK4 form failed to complement mpk4. Analysis of mpk4 expressing the SA hydroxylase NahG and of mpk4/npr1 double mutants indicated that SAR expression in mpk4 is dependent upon elevated SA levels but is independent of NPR1. PDF1.2 and THI2.1 gene induction by jasmonate was blocked in mpk4 expressing NahG, suggesting that MPK4 is required for jasmonic acid-responsive gene expression.

Alleles↗
PubMed2000

Structural studies of LNA:RNA duplexes by NMR: conformations and implications for RNase H activity.

We have used NMR and CD spectroscopy to study the conformations of modified oligonucleotides (locked nucleic acid, LNA) containing a conformationally restricted nucleotide (T(L)) with a 2'-O,4'-C-methylene bridge. We have investigated two LNA:RNA duplexes, d(CTGAT(L)ATGC):r(GCAUAUCAG) and d(CT(L)GAT(L)AT(L)GC):r(GCAUAUCAG), along with the unmodified DNA:RNA reference duplex. Increases in the melting temperatures of +9.6 degrees C and +8.1 degrees C per modification relative to the unmodified duplex were observed for these two LNA:RNA sequences. The three duplexes all adopt right-handed helix conformations and form normal Watson-Crick base pairs with all the bases in the anti conformation. Sugar conformations were determined from measurements of scalar coupling constants in the sugar rings and distance information derived from 1H-1H NOE measurements; all the sugars in the RNA strands of the three duplexes adopt an N-type conformation (A-type structure), whereas the sugars in the DNA strands change from an equilibrium between S- and N-type conformations in the unmodified duplex towards more of the N-type conformation when modified nucleotides are introduced. The presence of three modified T(L) nucleotides induces drastic conformational shifts of the remaining unmodified nucleotides of the DNA strand, changing all the sugar conformations except those of the terminal sugars to the N type. The CD spectra of the three duplexes confirm the structural changes described above. On the basis of the results reported herein, we suggest that the observed conformational changes can be used to tune LNA:RNA duplexes into substrates for RNase H: Partly modified LNA:RNA duplexes may adopt a duplex structure between the standard A and B types, thereby making the RNA strand amenable to RNase H-mediated degradation.

Base Sequence↗
PubMed2000

The siaA gene involved in capsule polysaccharide biosynthesis of Neisseria meningitidis B codes for N-acylglucosamine-6-phosphate 2-epimerase activity.

The capsule polysaccharide of Neisseria meningitidis serogroup B is composed of a homopolymer of alpha-2-->8 linked N-acetyl-neuraminic acid (sialic acid). The enzymes required for sialic acid biosynthesis and polymerization are encoded in region A of the capsule gene complex. We here describe the enzymatic activity of the siaA gene product as determined by biochemical analysis. siaA was overexpressed in Escherichia coli and the SiaA protein was purified to homogeneity. Enzymatic assays revealed that SiaA did not accept N-acetyl-glucosamine as substrate, but only N-acetyl-glucosamine-6-phosphate (EC 5.1.3.9). SiaA catalyzes the isomerization of N-acetyl-glucosamine-6-phosphate to form N-acetyl-mannosamine-6-phosphate. This reaction represents the first step in capsule biosynthesis of N. meningitidis B.

Acetylglucosamine↗
PubMed2000

Arabidopsis ATP A2 peroxidase. Expression and high-resolution structure of a plant peroxidase with implications for lignification.

Lignins are phenolic biopolymers synthesized by terrestrial, vascular plants for mechanical support and in response to pathogen attack. Peroxidases have been proposed to catalyse the dehydrogenative polymerization of monolignols into lignins, although no specific isoenzyme has been shown to be involved in lignin biosynthesis. Recently we isolated an extracellular anionic peroxidase, ATP A2, from rapidly lignifying Arabidopsis cell suspension culture and cloned its cDNA. Here we show that the Atp A2 promoter directs GUS reporter gene expression in lignified tissues of transgenic plants. Moreover, an Arabidopsis mutant with increased lignin levels compared to wild type shows increased levels of ATP A2 mRNA and of a mRNA encoding an enzyme upstream in the lignin biosynthetic pathway. The substrate specificity of ATP A2 was analysed by X-ray crystallography and docking of lignin precursors. The structure of ATP A2 was solved to 1.45 A resolution at 100 K. Docking of p-coumaryl, coniferyl and sinapyl alcohol in the substrate binding site of ATP A2 were analysed on the basis of the crystal structure of a horseradish peroxidase C-CN-ferulic acid complex. The analysis indicates that the precursors p-coumaryl and coniferyl alcohols are preferred by ATP A2, while the oxidation of sinapyl alcohol will be sterically hindered in ATP A2 as well as in all other plant peroxidases due to an overlap with the conserved Pro-139. We suggest ATP A2 is involved in a complex regulation of the covalent cross-linking in the plant cell wall.

Arabidopsis↗
PubMed2000

High carrier frequency of the 35delG deafness mutation in European populations. Genetic Analysis Consortium of GJB2 35delG.

Congenital deafness accounts for about 1 in 1000 infants and approximately 80% of cases are inherited as an autosomal recessive trait. Recently, it has been demonstrated that connexin 26 (GJB2) gene is a major gene for congenital sensorineural deafness. A single mutation (named 35delG) was found in most recessive families and sporadic cases of congenital deafness, among Caucasoids, with relative frequencies ranging from 28% to 63%. We present here the analysis of the 35delG mutation in 3270 random controls from 17 European countries. We have detected a carrier frequency for 35delG of 1 in 35 in southern Europe and 1 in 79 in central and northern Europe. In addition, 35delG was detected in five out of 376 Jewish subjects of different origin, but was absent in other non-European populations. The study suggests either a single origin for 35delG somewhere in Europe or in the Middle East, and the possible presence of a carrier advantage together with a founder effect. The 35delG carrier frequency of 1 in 51 in the overall European population clearly indicates that this genetic alteration is a major mutation for autosomal recessive deafness in Caucasoids. This finding should facilitate diagnosis of congenital deafness and allow early treatment of the affected subjects.

Connexin 26↗
PubMed2000

Low-threshold heat response antagonized by capsazepine in chick sensory neurons, which are capsaicin-insensitive.

The heat-transducing receptor VR1 cloned from rat sensory neurons can be activated by both noxious heat and capsaicin. As the response of sensory neurons to capsaicin is species dependent, it is conceivable that the responses to noxious heat and to capsaicin are transduced by distinct receptors across different species. Therefore, we investigated responses to noxious heat from a capsaicin-insensitive (chick) and a capsaicin-sensitive (rat) species. In chick, whole-cell patch-clamp experiments in isolated dorsal root ganglion neurons revealed two populations of neurons with different thresholds to noxious heat, activated at approximately 43 degrees C and approximately 53 degrees C. In cobalt uptake experiments, the proportion of neurons showing a heat-induced response increased with increasing heat stimuli. Application of capsaicin (1-10 microM) did not result in inward currents or cobalt uptake. Rat neurons yielded comparable results in heat experiments, but were capsaicin-sensitive. Although chick neurons are insensitive to capsaicin, the competitive capsaicin antagonist capsazepine (1-10 microM) was effective in blocking heat-induced responses, verified by patch-clamp and cobalt uptake methods. The noncompetitive capsaicin antagonist ruthenium red (10 microM) reduced to almost nil the proportion of heat-responsive neurons identified with the cobalt uptake method. These findings suggest that chick DRG neurons express a low-threshold heat-transducing receptor with a pharmacological profile distinct from the low-threshold heat receptor VR1 cloned from rat DRG neurons. The data support the idea that there might be heat receptor subtypes with differences in the capsaicin binding site.

Animals↗
PubMed2000

Cardioinhibition during tilt testing identifies patients who may benefit from pacing.

UNLABELLED: This study examined whether the various hemodynamic collapse patterns observed during tilt testing in patients with suspected neurocardiogenic syncope are relevant when planning therapy, particularly whether a predominantly cardioinhibitory response predicts a beneficial response from pacing. METHODS: The effects of temporary atrioventricular (A-V) sequential pacing were studied during tilt testing in 34 patients 48.2 +/- 18.5 years of age. The patient population was divided into a cardioinhibitory group (VASIS classes 2A and 2B) or mixed group (VASIS classes 1 and 3) according to their response to baseline tilt testing. The test was then repeated during A-V pacing with rate hysteresis. A positive response to A-V pacing was defined as a > or = 30-second increase between onset of symptoms and syncope, or mitigation of symptoms compared with the baseline tilt test. RESULTS: The study protocol was not successfully completed in three patients. Among the remaining 31 patients, a baseline cardioinhibitory response was observed in 17, and a mixed response in 14 patients. A-V sequential pacing was successful in 13 of 17 patients with a cardioinhibitory response versus 5 of 14 patients with a mixed response (P = 0.024). CONCLUSION: The presence of a predominantly cardioinhibitory collapse pattern (VASIS 2A and 2B) during baseline tilt testing doubled the likelihood of successful temporary A-V sequential pacing, and may identify patients with neurocardiogenic syncope most likely to benefit from permanent dual chamber pacing.

Blood Pressure↗
PubMed1999

Responses of neurons in the lateral thalamus of the cat to stimulation of urinary bladder, colon, esophagus, and skin.

In seven female alpha-chloralose-anesthetized cats, 52 lateral thalamic neurons were tested with noxious distension of the urinary bladder, the distal colon and the lower esophagus. In addition, the neurons were characterized with innocuous and noxious mechanical stimulation of the skin and deep structures. Of the 52 neurons tested, 32 (62%) were visceroceptive. Of these visceroceptive neurons, 20 (63%) were located in the periphery of the ventral posterolateral nucleus (VPLp), 10 (31%) in the adjacent posterior complex (PO), and two (6%) in the ventrolateral nucleus (VL). No differences were found with respect to location between neurons responsive or unresponsive to visceral stimulation. Ten neurons (31%) received input from more than one viscus and, therefore, showed viscerovisceral convergence. Excitatory or "inhibitory" responses were elicited by stimulation of the esophagus in 21 neurons, of the colon in 13, and of the urinary bladder in 11 neurons. No indications were found for a segregation of neurons responsive to a certain viscus and their location in VPLp or PO. Of 51 neurons, for which a somatic receptive field was determined, 44 (86%) exhibited low threshold type (LT), and seven (14%) wide dynamic range type (WDR) responses. The data indicate that there might exist a somatovisceral coregistration, because many neurons (69%) had homosegmental receptive fields, and bladder stimulation was the most successful stimulus. It is concluded that VPLp and the adjacent PO in the cat play a role in the perception and localization of painful events originating from thoracic and pelvic organs.

Animals↗
PubMed1999

Antisense RNA regulation in prokaryotes: rapid RNA/RNA interaction facilitated by a general U-turn loop structure.

Efficient gene control by antisense RNA requires rapid bi-molecular interaction with a cognate target RNA. A comparative analysis revealed that a YUNR motif (Y=pyrimidine, R=purine) is ubiquitous in RNA recognition loops in antisense RNA-regulated gene systems. The (Y)UNR sequence motif specifies two intraloop hydrogen bonds forming U-turn structures in many anticodon-loops and all T-loops of tRNAs, the hammerhead ribozyme and in other conserved RNA loops. This structure creates a sharp bend in the RNA phosphate-backbone and presents the following three to four bases in a solvent-exposed, stacked configuration providing a scaffold for rapid interaction with complementary RNA. Sok antisense RNA from plasmid R1 inhibits translation of the hok mRNA by preventing ribosome entry at the mok Shine & Dalgarno element. The 5' single-stranded region of Sok-RNA recognizes a loop in the hok mRNA. We show here, that the initial pairing between Sok antisense RNA and its target in hok mRNA occurs with an observed second-order rate-constant of 2 x 10(6) M(-1) s(-1). Mutations that eliminate the YUNR motif in the target loop of hok mRNA resulted in reduced antisense RNA pairing kinetics, whereas mutations maintaining the YUNR motif were silent. In addition, RNA phosphate-backbone accessibility probing by ethylnitrosourea was consistent with a U-turn structure formation promoted by the YUNR motif. Since the YUNR U-turn motif is present in the recognition units of many antisense/target pairs, the motif is likely to be a generally employed enhancer of RNA pairing rates. This suggestion is consistent with the re-interpretation of the mutational analyses of several antisense control systems including RNAI/RNAII of ColE1, CopA/CopT of R1 and RNA-IN/RNA-OUT of IS10.

Bacterial Proteins↗
PubMed1999

Identification of wheat varieties using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry and an artificial neural network

A novel tool for variety identification of wheat (Triticum aestivum L.) has been developed: an artificial neural network (ANN) is used to classify the gliadin fraction analysed by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOFMS). The robustness of this novel method with respect to various experimental parameters has been tested. The results can be summarised: (i) With this approach 97% of the wheat varieties can be classified correctly with a corresponding correlation coefficient of 1.0, (ii) The method is fast since the time of extracting gliadins from flour can be reduced to 20 min without significant decrease in overall performance, (iii) The storage of flour or extracts under standard conditions does not influence the classification ability (i. e. the generalisation ability) of the method, and (iv) The classification obtained is not influenced by the identity of the operator making the analysis. This study demonstrates that a combination of an ANN and MALDI-TOFMS analysis of the gliadin fraction provides a fast and reliable tool for the variety identification of wheat. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗
PubMed1999

Mortality patterns among electrical workers employed in the U.S. construction industry, 1982-1987.

BACKGROUND: Studies of electrical workers in the utility and manufacturing industries have reported excess site-specific cancer. No previous studies of electrical workers in the construction industry have been conducted. METHODS: Our study evaluated the mortality patterns of 31,068 U.S. members of the International Brotherhood of Electrical Workers who primarily worked in the construction industry and died 1982-1987. RESULTS: Comparison to the U.S. population by using the NIOSH life table showed significantly elevated proportionate mortality for many causes. Excess mortality for leukemia (proportionate mortality ratio (PMR)=115) and brain tumors (PMR=136) is similar to reports of electrical workers with occupational exposure to electric and magnetic fields in the electric utility or manufacturing industry. Excess deaths due to melanoma skin cancer (PMR=123) are consistent with findings of other PCB-exposed workers. A significantly elevated PMR was observed for the diseases caused by asbestos: lung cancer (PMR=117), asbestosis (PMR=247), and malignant mesothelioma (PMR=356) and from fatal injuries, particularly electrocutions (PMR=1180). The findings of statistically significant excess deaths for prostate cancer (PMR=107), musculoskeletal disease (PMR=130), suicide (PMR=113), and disorders of the blood-forming organs (PMR=141) were unexpected. CONCLUSIONS: Results suggest that more detailed investigations of occupational risk factors and evaluation of preventive practices are needed to prevent excess mortality in this hazardous occupation. Am. J. Ind. Med. 36:630-637, 1999. Published 1999 Wiley-Liss, Inc.

Adult↗
PubMed1999

Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48.

Using the monoclonal antibody C1.7, which recognizes a signaling, membrane-bound molecule on human NK and a proportion of CD8(+) T cells, we cloned a novel molecule we refer to as NK cell activation-inducing ligand (NAIL). It is a 365-amino acid protein that belongs to the immunoglobulin-like superfamily with closest homology to murine 2B4, and human CD84 and CD48. Using a soluble NAIL-Fc fusion protein, we determined the counterstructure for NAIL, CD48, which it binds with high affinity. Stimulation of human B cells with recombinant NAIL in the presence of a suboptimal concentration of human CD40 ligand or IL-4 resulted in increased proliferation. Treatment of human dendritic cells with soluble NAIL-leucine zipper protein resulted in an increased release of IL-12 and TNF-alpha. Using recombinant CD48 protein, we demonstrated the ability of this molecule to increase NK cell cytotoxicity and induce IFN-gamma production. We also showed that 2B4 binds to mouse CD48, suggesting that interaction of these receptors may play a similar role in both species. Taken together these results indicate that the NAIL-CD48 interaction may be an important mechanism regulating a variety of immune responses.

Amino Acid Sequence↗
PubMed1999

Expression of neurokinin-1 receptors on cultured dorsal root ganglion neurons from the adult rat.

The expression of neurokinin-1 receptors in isolated dorsal root ganglion neurons of adult rats was investigated using substance P covalently bound to a 1.4-nm gold particle. Binding of substance P-gold was determined in neurons after 0.8, 1.8 or 3.8 days under culture conditions. Substance P-gold binding sites were identified in 9.5 +/- 1.8% of the neurons that were cultured for 0.8 days. The proportion of neurons with substance P-gold binding sites increased to 21.5 +/- 3.6% after 1.8 days in culture and returned to the initial values (9.2 +/- 2.1%) after 3.8 days in culture. Binding of substance P-gold was suppressed by co-administration of [Sar9, Met(O2)11] substance P, a specific agonist at the neurokinin-1 receptor, but not by co-administration of [beta-Ala8] Neurokinin A (4-10), an agonist at the neurokinin-2 receptor, and senktide, an agonist at the neurokinin-3 receptor. This indicates that substance P-gold was bound specifically to neurokinin-1 receptors. Double-labelling with RT97, an antibody that selectively labels somata of A-fibres revealed that substance P binding sites were present in small neurons with myelinated and unmyelinated axons. These data show that a proportion of dorsal root ganglion neurons of adult rat in culture exhibit neurokinin-1 receptors. A transient increase in the proportion of neurons expressing neurokinin-1 receptors after 1.8 days in culture suggests that the expression of neurokinin-1 receptors is subjected to regulation.

Animals↗
PubMed1999

A non-pungent triprenyl phenol of fungal origin, scutigeral, stimulates rat dorsal root ganglion neurons via interaction at vanilloid receptors.

1. A [3H]-resiniferatoxin (RTX) binding assay utilizing rat spinal cord membranes was employed to identify novel vanilloids in a collection of natural products of fungal origin. Of the five active compounds found (scutigeral, acetyl-scutigeral, ovinal, neogrifolin, and methyl-neogrifolin), scutigeral (Ki=19 microM), isolated from the edible mushroom Albatrellus ovinus, was selected for further characterization. 2. Scutigeral induced a dose-dependent 45Ca uptake by rat dorsal root ganglion neurons with an EC50 of 1.6 microM, which was fully inhibited by the competitive vanilloid receptor antagonist capsazepine (IC50=5.2 microM). 3. [3H]-RTX binding isotherms were shifted by scutigeral (10-80 microM) in a competitive manner. The Schild plot of the data had a slope of 0.8 and gave an apparent Kd estimate for scutigeral of 32 microM. 4. Although in the above assays scutigeral mimicked capsaicin, it was not pungent on the human tongue up to a dose of 100 nmol per tongue, nor did it provoke protective wiping movements in the rat (up to 100 microM) upon intraocular instillation. 5. In accord with being non-pungent, scutigeral (5 microM) did not elicit a measurable inward current in isolated rat dorsal root ganglion neurons under voltage-clamp conditions. It did, however, reduce the proportion of neurons (from 61 to 15%) that responded to a subsequent capsaicin (1 microM) challenge. In these neurons, scutigeral both delayed (from 27 to 72 s) and diminished (from 5.0 to 1.9 nA) the maximal current evoked by capsaicin. 6. In conclusion, scutigeral and its congeners form a new chemical class of vanilloids, the triprenyl phenols. Scutigeral promises to be a novel chemical lead for the development of orally active, non-pungent vanilloids.

Animals↗
PubMed1998

Dialdehyde sesquiterpenes and other terpenoids as vanilloids.

Selected naturally occurring unsaturated dialdehyde sesquiterpenes and related bioactive terpenoids were assayed for vanilloid-like activity. Out of the 25 compounds tested, eight inhibited completely the specific binding of [3H]resiniferatoxin by rat spinal cord membranes: binding affinities ranged from 0.6 microM for cinnamodial to 19.0 microM for hebelomic acid F. These values were comparable to the binding affinity of capsaicin (2.7 microM). With the exception of four ligands, compounds that inhibited resiniferatoxin binding to rat spinal cord membranes were also pungent on the human tongue where they showed cross-tachyphylaxis with capsaicin. As expected from their reactive nature, these compounds possess additional sites of action, as reflected in the complex behavior of the stimulation of calcium influx by cinnamodial and cinnamosmolide at high concentrations. This observation might explain the unexpectedly weak membrane depolarization by cinnamodial compared to capsaicin. We conclude that a range of sesquiterpene dialdehydes and related terpenoids, both pungent and non-pungent, may function as vanilloids. These compounds may represent a new chemical lead for the development of vanilloid drugs, structurally unrelated to either capsaicin or resiniferatoxin.

Aldehydes↗