Metabolism of leukotriene B4 (LTB4) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) in human keratinocytes.
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12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
Biomedical subjects
J B Travers
Publications and source records attributed to J B Travers.
Hypoglossal neural activity during ingestion and rejection in the awake rat.
1. The activity of 34 hypoglossal (mXII) neurons was characterized during the ingestion and rejection of gustatory stimuli in the awake rat. Intraoral infusions of water, sucrose, sodium chloride, or hydrochloric acid initiated ingestion responses; infusions of quinine monohydrochloride initiated rejection responses. Electromyographic (EMG) activity from three oropharyngeal muscles monitored the occurrence of lick cycles and swallows (ingestion) and gape cycles (rejection). In addition, the orofacial region was videotaped to provide an independent assessment of lingual and jaw movements in relation to neural activity. 2. EMG activity during lick and gape cycles was quantified by calculating the duration, magnitude, and peak time of muscle contractions. Lick and gape cycles produced highly differentiated patterns of activity from jaw-opener (anterior digastric, AD), lingual protrudor (geniohyoid, GEN), and lingual retractor (styloglossus, STY) muscles. Lick cycles were characterized by an alternating two-phase sequence of protrusion-retraction; gape cycles by an initial coactivation of both lingual muscles (phase I), followed by a sequence of protrusion (phase II) and retraction (phase III). Contraction durations were significantly longer during gape cycles compared with lick cycles for the AD (Xlick +/- 59 ms; Xgape +/- 134 ms, means +/- SD), GEN (Xlick +/- 77 ms; Xgape +/- 200 ms), and STY (Xlick +/- 93 ms; Xgape +/- 220 ms) muscles. 3. Thirty-one out of 34 mXII neurons were functionally classified as protrudor- or retractor-related by cross-correlating anterior digastric EMG activity with neural activity during licking. Fourteen out of 34 neurons were protrudor-related, 17/34 were retractor-related. These classifications were largely consistent with the results from an analysis of a subset of cells (n = 14) that directly compared neural activity with videotaped records of visible tongue movements. 4. The magnitude of mXII activity during ingestion and rejection was compared by determining the mean number of spikes per lick, gape, and swallow for each neuron. Five out of 14 (36%) protrudor-related and 10/17 (59%) retractor-related cells had significant increases in activity during gape responses compared with the number of spikes per lick cycle. This increased activity of mXII neurons was consistent with the more robust lingual motor activity during the gape response. Two protrudor-related and three retractor-related neurons showed significant decreases in activity during gape responses. Although a similar proportion of mXII neurons exhibited decreases in activity during swallows compared with licks (3 protrudor- and 1 retractor-related), fewer mXII neurons (1 protrudor- and 1 retractor-related) showed increased activity during swallows.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Gustatory and tactile stimulation of the posterior tongue activate overlapping but distinctive regions within the nucleus of the solitary tract.
Both the gustatory and somatosensory systems provide necessary sensory input for the initiation and control of oromotor behaviors. Behavioral studies indicate that somatosensory input from the posterior tongue (PT) is important in initiating swallowing, whereas PT taste input is particularly important in gustatory rejection reflexes. However, there have been few studies of the central representation of PT gustatory or tactile responses. In the present study, electrophysiological multi-unit recording techniques were used to map the location of PT-mediated taste and tactile responses in the nucleus of the solitary tract (NST) of the rat. A stimulation technique that allows taste stimuli to be introduced directly and specifically into the papillae trenches was used to optimally activate PT taste receptors located within the circumvallate (CV) and foliate (FOL) papillae. The results demonstrated that non-PT responsive sites dominated the rostral half of the rostral division of NST (rNST), while PT-responsive sites dominated the caudal half. Some PT-responsive sites extended into the caudal NST. Both gustatory and tactile stimuli were effective at 28% of PT-responsive locations (taste-tactile sites), whereas at the remaining locations, only tactile stimulation was effective (tactile-only sites). Although these two types of PT-responsive sites exhibited some anatomical overlap, their distributions were distinctive, with taste-tactile sites restricted medially and the laterally located tactile-only sites offset caudally. On the other hand, responses arising from stimulation of the CV and FOL exhibited no anatomical organization, i.e., responses to stimulation of both papillae were coexistensive. On average, of the four tastants used (0.01 M Na saccharin, 0.3 M NaCl, 0.01 M quinine hydrochloride, 0.03 M HCl), HCl was the most effective stimulus for both the CV and FOL. The present results delimit the regions of the NST that provide a substrate for the gustatory and somatosensory limbs of PT-mediated oromotor reflexes.
Animals↗
The contribution of gustatory nerve input to oral motor behavior and intake-based preference. I. Effects of chorda tympani or glossopharyngeal nerve section in the rat.
Two-bottle intake tests and taste reactivity (TR) tests were used to reveal whether changes in ingestive behavior would follow bilateral section of either the chorda tympani (CT) or the glossopharyngeal (GP) nerve. Rats received two-bottle intake tests to compare 24-h ingestion of water to that of NaCl, MgCl2, quinine, or sucrose. Prior to each long-term intake test, rats received a 1 min, 1 ml intraoral infusion of the same chemical stimulus. Ingestive and aversive oral motor responses elicited by these 1 ml infusions were videotaped and subsequently analyzed. GP-section did not alter quinine or sucrose preference; overall, preference of MgCl2 and NaCl was also similar to controls. In contrast, TR tests in GP-sectioned rats revealed that most quinine, MgCl2 and NaCl stimuli elicited significantly fewer aversive oral motor responses. In addition, the latency of aversive responses to these 3 chemical stimuli was increased for these rats. Intake-based preference tests failed to show any difference between rats with CT nerve section and controls. In TR tests, however, CT-sectioned rats displayed significantly fewer ingestive oral motor responses to NaCl, MgCl2, and quinine than controls. Neither sucrose intake nor sucrose-elicited TR were altered by CT or GP nerve section. This report confirms the failure of long-term intake tests to uncover behavioral deficits following the section of gustatory nerves. In contrast, the use of a different behavioral test makes clear for the first time that gustatory nerve section has dramatic consequences on ingestive behavior. The examination of taste elicited oral motor behaviors reveals a coherent and nerve specific pattern of neurological deficit following peripheral nerve section.
Animals↗
Binding of carbamyl-platelet-activating factor to the Raji lymphoblast platelet-activating factor receptor.
Carbamyl-platelet-activating factor (1-hexadecyl-2-N-methylcarbamyl-glycero-3-phosphocholine; CPAF) is an analog of platelet-activating factor (PAF) containing an N-methylcarbamyl moiety at the sn-2 position. CPAF was tested for effects on the Raji lymphoblast PAF receptor. Binding studies conducted at 4 degrees C demonstrated specific binding that reached saturation within 60-80 min. Scatchard analysis of CPAF binding data revealed a single class of CPAF binding sites (14,800/cell) with a K = 2.9 +/- 0.9 nM. Competition binding studies with PAF indicated that CPAF has about one-third the potency of native PAF. Unlike PAF, however, CPAF was not significantly metabolized by Raji lymphoblasts at 37 degrees C. CPAF was shown to have PAF-agonistic qualities, since 100 pM to 1 microM CPAF increased free intracellular calcium in a dose-dependent manner. The structurally dissimilar PAF receptor antagonists CV-6209 and alprazolam inhibited the CPAF-induced calcium changes at doses that competed with CPAF binding. Treatment of Raji lymphoblasts with PAF or CPAF (10 pM-1 microM) did not affect spontaneous proliferation, suggesting that the PAF receptor is not involved in the proliferative process in this cell line. These studies demonstrate that CPAF is a metabolically stable lymphoblast PAF receptor agonist that may provide a useful tool in the further elucidation of the role of PAF in lymphocyte function.
Burkitt Lymphoma↗
Hypoglossal neural activity during licking and swallowing in the awake rat.
1. Thirty-five neurons in the hypoglossal nucleus (mXII) of the rat were characterized during licking and swallowing in response to fluid stimulation in an awake, freely moving preparation. Simultaneously recorded electromyographic (EMG) recordings from a subset of oropharyngeal muscles were obtained to delineate both the lick cycle and the occurrence of swallows. Most mXII neurons discharged with rhythmic bursts in phase with licking. Twenty-six of the 35 mXII neurons had bimodal interspike interval (ISI) histograms, reflecting rhythmic bursts and the absence of spontaneous activity. Three mXII cells with unimodal ISI histograms were rhythmically active during licking but had some spontaneous activity. Of the remaining six cells with unimodal ISI histograms, five had nonbursting modes of activity. 2. Phase relationships between neural and EMG activity during licking were determined by cross-correlation and compared with distributions of cross-correlations between lingual and masticatory EMG activity. A bimodal distribution of cross-correlations was obtained by cross-correlating EMG activity between lingual protrudor muscles [genioglossus (GG) or geniohyoid (GH)] and masticatory jaw-opener activity [anterior digastric (AD)] and cross-correlating lingual retractor activity [styloglossus (STY)] with anterior digastric EMG. A similar bimodal distribution of cross-correlations obtained between mXII neuron activity and AD contractions suggested that the majority of mXII neurons (30/35) could be classified as protrudor- or retractor-related. Neurons classified as protrudor-related cells were located ventrally in mXII; cells classified as retractor-related were more dorsally located, consistent with anatomic and physiological descriptions of the myotopic organization of mXII. 3. Ten mXII protrudor-related neurons responded with a mean of 4.9 +/- 2.2 (SD) action potentials per lick cycle and preceded the peak jaw-opening phase of licking by a mean of 22.3 ms. In contrast, the activity of 20 retractor-related mXII neurons lagged the jaw-opening phase of licking by a mean of 55.9 ms, with a mean of 5.5 +/- 3.4 (SD) action potentials occurring per lick cycle. Five other mXII neurons exhibited nonrhythmic activity during licking and could not be classified as protrudor- or retractor-related on the basis of cross-correlations with the AD. 4. The occurrence of a swallow decreased the licking frequency by 21%, corresponding to an increase of approximately 43 ms in the period between AD contractions.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Evidence for platelet-activating factor receptors in several B lymphoblastoid cell lines.
Previous studies have shown that Raji, an Epstein-Barr virus (EBV)-immortalized Burkitt lymphoma B cell line, contains functional platelet-activating factor (PAF) receptors. Twelve other lymphoid cell lines, including Burkitt and non-Burkitt B cell lines, T cell lines, and a non B, non T cell line were tested for the presence of PAF receptors. Radioligand binding studies conducted at 4 degrees C revealed that six lymphoid cell lines of B cell origin (Raji, P3HR-1, BJAB, BJA/HR-1, Dakiki and PB-1) could specifically bind [3H]PAF. Treatment of four (Raji, P3HR-1, Dakiki and PB-1) of the above lymphoid cell lines with PAF resulted in an increase in free intracellular calcium, indicating that these specific PAF binding sites were functional PAF receptors. Other B cell lines (Daudi, B95-8, sfBT, CB-1), T cell lines (MOLT-4, CCRF-CEM) and a non B, non T cell line (NALM-6) had no PAF binding sites and showed no PAF-induced increase in intracellular calcium levels. These studies demonstrate evidence for the presence of PAF receptors on several B lymphocyte cell lines.
Animals↗
Metabolism of 15-hydroxy-5,8,11,13-eicosatetraenoic acid by MOLT-4 cells and blood T-lymphocytes.
MOLT-4 lymphocytes metabolize 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) via beta-oxidation with retention of the hydroxyl group at the omega 6-carbon atom. 15-HETE oxidation is accompanied by the time-dependent accumulation of both beta-hydroxy acids and metabolites produced by repetitive cycles of the beta-oxidation spiral. Detection of 7-hydroxy-5-dodecenoic acid shows that these cells continue to beta-oxidize the substrate when the conjugated diene is allylic to a hydroxyl group. When 15-HETE was the substrate, it was also possible to detect 12-hydroxy-5,8,10-heptadecatrien-1-al and 3,15-dihydroxy-8,11,13-eicosatrienoic acid. The former product may be produced by alpha-oxidation of 13-hydroxy-6,9,11-octadecatrienoic acid followed by its decarboxylation. Detection of a 20-carbon metabolite, lacking a double bond at position 5, suggests that an intermediate of beta-oxidation was used as a substrate for chain elongation. When 13-hydroxy-6,9,11-octadecatrienoic acid was used as a substrate, it was indeed possible to detect 3,15-dihydroxy-8,11,13-eicosatrienoic acid as well as 15-hydroxy-8,11,13-eicosatrienoic acid. In addition, 13-hydroxy-6,9,11-octadecatrienoic acid was a precursor for the biosynthesis of both 14-hydroxy-7,10,12-nonadecatrien-1-al and 1,14-dihydroxy-7,10,12-nonadecatriene. These studies with MOLT-4 cells as well as with T-lymphocytes isolated from blood show that products of the 15-lipoxygenase pathway are metabolized with the accumulation of a variety of compounds. Since 15-HETE has been implicated as a modulator of T-cell function, these findings raise the possibility that the newly described metabolites may be involved in regulating lymphocyte function.
Adult↗
The metabolism of platelet-activating factor in human T-lymphocytes.
The metabolism of 1-[3H]alkyl-2-acetyl-sn-glycero-3-phosphocholine (1-[3H]alkyl-2-acetyl-GPC; platelet-activating factor; PAF) was investigated in purified human peripheral blood T-lymphocytes and a human leukemia cell line of T-cell origin (MOLT-4). The major metabolic products of T-lymphocyte PAF metabolism are 1-alkyl-2-acyl-GPC, 1-alkyl-2-lyso-GPC and neutral lipid. The pattern of PAF metabolism in peripheral blood T-lymphocytes and MOLT-4 lymphoblasts was similar, although MOLT-4 lymphoblasts transformed PAF to 1-alkyl-2-acyl-GPC faster than peripheral blood T-lymphocytes (67% vs. 21% of added label after 64 min at 37 degrees C, respectively). Pre-exposure of MOLT-4 lymphoblasts to 1 mM of the serine hydrolase inhibitor phenylmethylsulfonyl fluoride resulted in an inhibition of PAF metabolism. Our results indicate that intact T-lymphocytes actively metabolize this biologically active phospholipid by the deacetylation-transacylation pathway.
Cell Line↗
Identification of functional platelet-activating factor receptors in Raji lymphoblasts.
The binding and metabolism of platelet-activating factor (PAF) were characterized in Raji, a human Burkitt's lymphoma-derived cell line. Raji lymphoblasts readily metabolized PAF by deacetylation-reacylation at 37 degrees C, but not at 4 degrees C. Binding studies conducted at 4 degrees C demonstrated specific binding that reached saturation within 80 min. This binding was only partially reversible. Scatchard analysis of PAF binding data revealed a single class of PAF binding sites (17,800 +/- 3,600/cell) with a K of 2.3 +/- 0.3 nM. These high-affinity PAF binding sites were shown to be functional receptors, as 100 pM to 1 microM PAF increased free intracellular calcium in a dose-dependent manner. The dose of PAF necessary to achieve half maximal calcium mobilization response was 6.3 nM, which was in the range of the K for the receptor calculated from the binding studies. The structurally dissimilar PAF receptor antagonists CV-3988 and BN52021 inhibited the PAF-induced calcium changes at doses that competed with PAF binding. These studies provide the first evidence for a functional PAF receptor expressed on a lymphocyte cell line.
B-Lymphocytes↗
Platelet-activating factor stimulates phosphatidylinositol hydrolysis in the rat myometrium.
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Animals↗
Efferent projections from the anterior nucleus of the solitary tract of the hamster.
The efferent projections from the anterior nucleus of the solitary tract (NST) of the golden hamster (Mesocricetus auratus) were determined using both anterograde and retrograde techniques. Injections of [3H]leucine were made into the anterior NST in regions responsive to gustatory stimulation of the anterior tongue. Ascending projections to the parabrachial nuclei (PBN) were evident as were projections within the NST and subjacent reticular formation. The cells of origin for both ascending and descending pathways were characterized by deposits of HRP into the PBN and caudal medulla. Cells projecting to the PBN were located in the dorsal and dorsolateral anterior NST in contrast to cells from the ventral region of the anterior NST which project within the medulla. Neurons in the reticular formation ventral to the anterior NST project to both regions. These local projections adjacent to oral motor nuclei provide an anatomical basis for the anterior nucleus of the solitary tract to influence oro-motor responses.
Animals↗
The effects of glossopharyngeal and chorda tympani nerve cuts on the ingestion and rejection of sapid stimuli: an electromyographic analysis in the rat.
The present study tested the effects of bilateral section of either the chorda tympani or glossopharyngeal nerves on the production of oro-pharyngeal electromyographic (EMG) responses to intra-oral sapid stimulation. The responses of adult rats fitted with intra-oral cannulas and fine-wire electrodes in the anterior digastric (jaw opening) and thyropharyngeus (swallowing) muscles were examined following direct oral stimulation with water and 5 concentrations of sucrose, NaCl, and quinine monohydrochloride (QHCl). One group of rats was tested both before and after bilateral removal of the chorda tympani. A second group of rats was tested subsequent to bilateral removal of the glossopharyngeal nerves. A normal EMG response pattern to suprathreshold QHCl consisted of several intra-oral licks followed by a series of large amplitude mouth openings (gapes). In addition, there was a longer latency to the first swallow following QHCl stimulation compared to water stimulation. Cutting either nerve affected this rejection response to QHCl, but produced little change in the ingestive response to the other stimuli. Following chorda tympani nerve cuts, rats showed an increased latency to the first gape and a small reduction in the number of gapes across the 5 concentrations of QHCl (16%). In contrast, bilateral section of the glossopharyngeal nerves produced a much larger reduction in the number of gapes (54%), but had no effect on the latency to the first gape. In addition, the latency to swallow suprathreshold QHCl was shorter following glossopharyngeal nerve cuts. These observations suggest that gustatory receptors on the anterior tongue, innervated by the chorda tympani, initiate a rejection response, but that receptors on the posterior tongue, innervated by the glossopharyngeal nerve, are necessary for a sustained rejection sequence.
Administration, Oral↗
Gustatory neural processing in the hindbrain.
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Animals↗
Electromyographic analysis of the ingestion and rejection of sapid stimuli in the rat.
Previous behavior studies (Grill & Norgren, 1978) demonstrated that gustatory stimuli produce stereotyped orofacial movements that constitute the observable concomitants of ingestion and rejection. For further clarification of the relation between these orofacial movements (the buccal phase of ingestion) and the act of swallowing (the pharyngeal phase), electromyographic responses to intraoral sapid stimulation were recorded from a subset of orofacial and pharyngeal muscles in a freely moving chronic preparation. Activity in a jaw opening muscle (anterior digastric), a facial muscle (zygomatic), tongue protruder (genioglossus), tongue retractor (styloglossus), and a pharyngeal constrictor used in swallowing (thyropharyngeus) differentiated between ingestive sequences to water (W), sucrose (S), and NaCl (N) and a rejection response elicited by quinine monohydrochloride (Q). Ingestion responses to W, S, and N consisted of rhythmic alterations between genioglossus and styloglossus activity (intraoral licks) accompanied by episodic bursts of pharyngeal constrictor activity (swallowing). Both bout duration and the number of swallows increased at higher concentrations of S and N. In contrast, Q stimulation elicited a rejection response, characterized by several licks and followed by long duration contractions of the zygomatic and anterior digastric muscles (gapes). During gapes, styloglossus activity rather than genioglossus activity was simultaneous with that of the anterior digastric. At higher concentrations of Q, the latency to gape decreased and the latency to swallow increased. The earliest components of the response to S, N, or Q were virtually indistinguishable from one another, results suggesting that tactile (fluid) stimulation initiates the ingestive sequence and that gustatory stimuli modulate this ongoing activity.
Animals↗
Afferent projections to the oral motor nuclei in the rat.
Projections to the trigeminal, facial, ambiguus, and hypoglossal motor nuclei were determined by using horseradish peroxidase histochemistry. Most of the afferent projections to these motor nuclei were from the brainstem reticular formation, frequently in areas adjacent to other synergetic motor nuclei. The reticular formation lateral to the hypoglossal nucleus and reticular structures surrounding the trigeminal motor nucleus projected to each of these other brainstem motor nuclei involved in oral-facial function. Afferent projections to these motor nuclei also were organized along the rostrocaudal axis. Within the reticular formation most of the afferent projections to the trigeminal motor nucleus originated rostral to the majority of neurons projecting to the hypoglossal and ambiguus nuclei, which in turn were rostral to the primary source of reticular afferents to the facial nucleus. In comparison, projections from the sensory trigeminal nuclei and nucleus of the solitary tract were sparse. The interneuron pools that project to the orofacial motoneurons provide one further link in understanding the brainstem substrates for integrating oral and ingestive behaviors.
Afferent Pathways↗
Gustatory neuron types in hamster brain stem.
In general, mammalian taste neurons are broadly responsive to stimuli representing different taste qualities. In the hamster, this breadth of tuning increases systematically from peripheral to successively higher brain stem neurons. Some investigators have classified taste-responsive neurons into "best-stimulus" categories on the basis of which of the four basic stimuli (sucrose, NaCl, HCl, or quinine hydrochloride) elicits the maximum response. However, attempts by others to demonstrate the existence of taste neuron types in the chorda tympani nerve and medulla of the rat using hierarchical cluster analysis have not been successful, resulting in the conclusion that there are no neuron types in the rat gustatory system. The present study was designed to look at the question of neuron types in the hamster, a species with a broader range of gustatory sensitivities to anterior tongue stimulation. Responses of 30 neurons in the nucleus tractus solitarius (NTS) and 31 neurons in the parabrachial nuclei (PbN) of the hamster to an array of 18 stimulus compounds were recorded extracellularly. The similarities of the neural response profiles of these cells at each synaptic level were compared using multivariate statistical techniques. The possiblee grouping of cells on the basis of similarities in their response functions was examined with hierarchical cluster analysis, and the relationships among these response functions were examined with multidimensional scaling. The results of the cluster analysis suggested that at both the NTS and PbN, there are three clusters of neural response profiles. These three clusters of response profiles are characterized at both synaptic levels by their predominant sensitivity to 1) sucrose and other sweet-tasting compounds, 2) sodium salts, and 3) nonsodium salts and acids. Representation of these neurons in a two-dimensional space yielded three nonoverlapping groups of cells in both the NTS and PbN, corresponding to the three groups identified by the hierarchical cluster solution. Classification of taste neurons either by their best stimulus or by other criteria has been criticized on the grounds that it may constitute an arbitrary division of a continuous population of neurons. The techniques of numerical taxonomy, which take the cells' variability into account, also result in a grouping of taste cells into classes. These taxonomic classes agree in most instances (80% in NTS and 80.6% in PbN) to a best-stimulus classification. The failure of some investigators to find types of neural response profiles in the rat gustatory system may be the result of species differences in taste sensitivity as well as differences in the statistical procedures employed.
Acids↗
Coding of taste stimuli by hamster brain stem neurons.
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Acids↗