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Among the cells in the blood vascular system, platelets in mammals and thrombocytes in lower vertebrates are the source of crucial mediators in hemostatic functions. Although these cells have been known to be primarily involved in thrombosis and hemostasis, platelets and thrombocytes have been shown recently to have roles in inflammatory functions and the immune response in general. Thrombocytes/platelets are widely recognized contributors to inflammatory responses upon stimulation with various microbial stimulants. In recent years, the role of platelets has been shown in adaptive immune responses. Therefore, thrombocytes/platelets should be considered as specialized immune cells that not only resemble innate effector cells in function but also have a role in affecting adaptive immunity through cellular contact and interaction with antigen presenting cells and lymphocytes., (Copyright © 2014 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Prostaglandin D(2) (PGD(2)) is produced by a variety of immune and non-hematopoietic cells and appears to function in both an inflammatory and homeostatic capacity. Two genetically distinct PGD(2)-synthesizing enzymes have been identified to date, including hematopoietic- and lipocalin-type PGD synthases (H-PGDS and L-PGDS, respectively). Though the inter-species expression profiles of these two enzymes vary widely, H-PGDS is generally localized to the cytosolic aspect of immune and inflammatory cells, whereas L-PGDS is more resigned to tissue-based expression. PGD(2) activity is principally mediated through two unique G protein-coupled receptors (GPCR), designated DP(1) and DP(2). These receptors exhibit overlapping binding profiles, yet their respective agonists elicit generally distinctive responses. Additional to DP receptors, the PGD(2) metabolite 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) binds the nuclear peroxisome proliferator-activated receptor gamma (PPARgamma) and has the facility to initiate a variety of anti-inflammatory phenotypes either through or independent of PPARgamma association. This review highlights the collective relevance of PGD(2) and its respective synthases, receptors, and metabolites in immunopathologic responses.

An alert cynomolgus macaque was fed a sweet solution to satiety as the activity of a gustatory neuron in the amygdala was recorded to that solution and to four other taste stimuli. This experiment was conducted a total of 14 times in two monkeys. The responses of individual neurons to the satiety stimuli were suppressed by as little as 1%, and as much as 100% by the induction of satiety (mean suppression = 58%). Nine of the 14 cells responded to the satiety solution with excitation, and their responses were suppressed by a mean of 62% by satiety. Five neurons responded with inhibition, and their responses were suppressed by a mean of 50%. Responses to other taste stimuli, not associated with satiety, were affected to a lesser extent. The amygdala is a taste relay between the primary gustatory cortex, where satiety has no influence on responses to taste stimuli, and the lateral hypothalamic area where the effect of satiety is total. The data presented here indicate that the amygdala is a functional as well as anatomical intermediary between these two areas, and serves as a stage in the process through which sensory stimuli are imbued with motivational significance.

Rats show a pronounced preference for the tastes of starch-derived polysaccharides. Three of these compounds--Polycose, maltotriose and amylopectin--were used along with a standard array of chemicals in a study of their effectiveness as taste stimuli, as monitored by evoked single unit activity in the nucleus tractus solitarii (NTS). Maltotriose and amylopectin elicited very few spikes and no clear quality-related pattern of neural activity. Polycose, however, was an effective taste stimulus. It evoked an activity profile across neurons and over time that was poorly correlated with that of the prototypical sugar (sucrose) and only moderately related to those of the non-sugar prototypes (NaCl, HCl and quinine-HCl). The 14 cells (23%) that responded particularly well to Polycose were all members of neuronal subgroups that emphasized salt, acid and quinine sensitivity. Thus, despite the strong behavioral preference shown to Polycose, its neural profile is unlike those of other preferred stimuli. Polycose may represent a unique taste stimulus whose quality cannot be readily associated with those of the traditional 4 basic tastes.

Amiloride is an inhibitor of passive sodium transport. Its application to taste receptors blocks inward sodium current, suppresses sodium-induced neural activity and reduces the perceived intensity of NaCl. We recorded taste-evoked responses of single neurons in the nucleus tractus solitarius (NTS) of the rat before and after the lingual application of amiloride to determine which neurons would be affected, the degree of the effect and the subsequent form of the neural code for sodium. Responses to all 7 stimuli that contained Na+ or Li+ were suppressed by amiloride. Activity evoked by the 8 other stimuli was unaltered. NTS neurons could be divided into 4 subsets according to their response profiles: Group 1 (salt-sugar), Group 2 (salt), Group 3 (salt-acid) and Group 4 (acid-salt-bitter). The entire effect of amiloride was discharged on cells in Groups 1 and 2; those in Groups 3 and 4 were unaffected. Following amiloride application, the neural code for sodium and lithium salts was highly similar to those for acids, bitter salts and quinine. Thus the activity of neurons in Groups 1 and 2 may be responsible for the distinction between 'saltiness' and sour-bitter tastes. The results imply that specific receptors are responsible for the recognition and transduction of sodium salts and that this specificity is maintained in the peripheral taste nerves to be manifested in the NTS.

The ingestive behavior of decerebrate rats has been studied for some time, yet little is known of its neural substrates. While taste fibers in rats proceed from hindbrain to thalamus and ventral forebrain, these regions return centrifugal fibers to the hindbrain by which lower-order taste activity may be influenced. We examined the functional characteristics of taste neurons in the nucleus tractus solitarii (NTS) of chronic decerebrate rats in which this reciprocal communication was disrupted and compared them with those of intact controls. Nine Wistar rats were decerebrated at the supracollicular level. After a minimum of one week recovery, they were immobilized with Flaxedil, anesthetized locally and prepared for recording. The responses of 50 taste cells were isolated bilaterally from the NTS of these animals, while the activity of 50 additional neurons was recorded from 12 intact rats under the same conditions. Taste stimuli included 7 Na-Li salts, 3 sugars, HCl and citric acids, quinine HCl and NaSaccharin. Mean spontaneous activity in decerebrates was 6.5 spikes/s, 36.0% lower than the level in intact animals. Mean evoked activity was reduced by 32.6%. Analyses of the effects of stimulus quality, intensity and time course of the responses all indicated that the decrease in activity was attributable to the inability of taste cells in decerebrate rats to respond to demands for high discharge rates. This deficit could be responsible for the failure of these animals to develop conditioned taste aversions. Neurons from decerebrate preparations did, however, retain the broad sensitivity across stimuli that characterized taste cells in intact preparations. It was also typical that most neuron response profiles from decerebrates could be grouped into 3 loose clusters with peak sensitivities to acid-salt, salt or sugar. An analysis of similarities among stimulus activity profiles indicated that Na-Li salts, sugars and an acid-quinine complex represented 3 groups of stimulus quality; in intact animals, the primary distinction was between sweet and non-sweet stimuli. Moreover, the response to sodium saccharin lost its bitter component in decerebrates. These findings were in general agreement with those derived from acute decerebrate rats.

Attempts to define the organization of the taste system in terms of the physical characteristics of stimuli have been largely unsuccessful. We recorded taste-evoked neural activity in the rat's hindbrain and determined that stimuli could be effectively organized along a physiological dimension which corresponds to stimulus toxicity. Taste is a visceral sense that mediates between the external and internal chemical environments. Its responsiveness to a wide range of chemicals and its organization along a dimension which promotes the organism's physiological welfare ideally suit it to that purpose.

Third-order neurons from the pontine taste area (PTA) were analyzed in accordance with the across-fiber pattern theory of gustatory neural coding. Single neuron responses, evoked by chemical stimulation of the tongue, were recorded from the PTA of acute Nembutalized rats. They reveal that PTA neurons are broadly sensitive to stimuli representing the 4 putative basic taste qualities. Of 35 neurons, 33 responded to at least 3 of the 4 quality classes. Time course analyses indicate that stimuli which are shown to be alike in behavioral studies exhibit similar temporal response sequences. Correlations between all possible pairs of response patterns indicate that like-tasting chemicals elicit similar profiles of activity across the neural population. A multidimensional analysis indicates that three underlying physico-chemical dimensions (as yet undefined) bear upon the neural responses. In certain of their response properties, PTA neurons are like those of the (second-order) solitary nucleus; in other respects they auger the characteristics seen in the (fourth-order) thalamic neurons. It is concluded that the PTA is functionally as well as anatomically intermediate between the solitary nucleus and thalamus in the taste processing chain.

Two experiments were performed in rats to evaluate the relative taste qualities of 12 L-amino acids, each at a concentration which evoked half the maximum response for that chemical. The first study involved recording the activity of 40 individual chorda tympani fibers to the stimulus series. Only 34% of the evoked responses resembled the short latency phasic-tonic activity which characterizes gustatory responses to inorganic salts and acids. 32% had latencies exceeding 1 s; another 27% consisted of only a phasic burst lasting less than 1 s. The remaining 7% were inhibitory. Both long latency and purely phasic activity were stimulus selective: 61% of the former were in response to Gly or Pro while 69% of the latter were evoked by Cys-HCl, Lys-HCl or His. Response inhibition was not associated with either specific fibers or stimuli. Thus amino acids, which to humans represent a class of perceptually complex stimuli, show a corresponding complexity of evoked neural properties in the rat. The second study employed a conditioned taste aversion paradigm to assess the qualitative similarity of each amino acid to the others and to the 4 prototypical taste stimuli; NaCl, HCl, quinine-HCl and sucrose. Some amino acids showed strong generalization to a single gustatory prototype (Pro and Gly to sucrose; Cys-HCl to HCl); others generalized well to multiple prototypes (e.g. Arg to sucrose and NaCl). Several showed poor generalization to all 4 prototypical tastes, calling into question the assumption that these 4 totally encompass the gustatory domain.

Feeding to satiety decreases the acceptability of the taste of food. In order to determine whether the responsiveness of gustatory neurons in the nucleus tractus solitarius (NTS) is influenced by hunger, neural activity in the NTS was analyzed while monkeys were fed to satiety. Gustatory neural activity to glucose, fruit juice, NaCl, HCl and quinine HCl was measured before, while and after the monkey was fed to satiety with glucose, fruit juice or sucrose. While behavior turned from avid acceptance to active rejection upon repletion, the responsiveness of NTS neurons to the stimulus array, including the satiating solution, was unmodified. It is concluded that at the first central synapse of the taste system of the primate, neural responsiveness is not influenced by the normal transition from hunger to satiety. This is in contrast to the responses of a population of neurons recorded in the hypothalamus, which only occur to the taste of food when the monkey is hungry. Thus, NTS gustatory activity appears to occur independently of normal hunger and satiety, whereas hypothalamic neuronal activity is more closely related to the influence of motivational state on behavioral responsiveness to gustatory stimuli.

The physiological importance of L-amino acids implies that the gustatory system should be sensitive to their presence in the environment. This notion is reinforced by research showing that rats are able to self-regulate their dietary consumption of amino acids and other important nutrients. This paper describes two studies which begin a systematic evaluation of the neural and behavioral effects of L-amino acids on gustation in the rat. The first experiment defined the neural thresholds, intensity-response functions and time courses of whole chorda tympani nerve responses to 12 stimuli. Thresholds varied from 10(-4) M (arginine) to 8 X 10(-2) M (proline), with pH-related amino acids being low and those reported by humans to be sweet being high. Maximum neural effectiveness, relative to the resting level of neural activity, ranged from 108% (2.0 M lysine-hydrochloride) to 8% (0.1 M leucine), with pH-related stimuli evoking the greatest activity. Neural time courses were varied, and often did not include well-defined phasic and tonic components. The second experiment measured the rat's preferences in 24-h two-bottle tests. Preference thresholds were typically lower than neural thresholds, presumably due to extra-chorda tympani input involved in the perception of flavor. They ranged from 2 X 10(-6) M (methionine) to 6 X 10(-2) m (leucine) and were in good agreement with psychophysically defined humar thresholds. Seven stimuli were preferred at low concentrations, but only two (alanine, leucine) continued to be appetitive as intensity increased. Preferences were predictable for 10 of the 12 stimuli from psychophysical reports. Rats also rejected amino acids in direct proportion to their toxicity, demonstrating the protective function of the taste-hedonic system.