Suppression of salt intake in the rat by neurokinin A: comparison with the effect of kassinin

The present study investigates the effect of the mammalian tachykinin neurokinin A on salt intake in the rat. Intracerebroventricular injection of neurokinin A inhibited salt intake elicited by sodium depletion, by subchronic deoxycorticosterone treatment and by adrenalectomy. It also inhibited the need-free salt intake of female rats that had been previously depleted of sodium. Since different brain mechanisms elicit salt intake in these experimental models, it is concluded that neurokinin A exerts a general antinatriorexic effect. Apparently, its inhibitory effect on salt intake is not due to malaise or competing behaviors, as shown by the fact that the doses of neurokinin A which suppress salt intake do not suppress milk intake. In comparison to the amphibian tachykinin kassinin, neurokinin A possesses a similar spectrum of antinatriorexic activities, but is markedly less potent and less effective in all the experimental models investigated. These findings suggest that activation of neurokinin A receptors cannot solely account for the potent antinatriorexic effect of kassinin and of other nonmammalian tachykinins.     

Ontogeny of the novel tachykinins neurokinin A, neurokinin B and neuropeptide K in the rat central nervous system

Neurokinin A, neurokinin B and neuropeptide K content has been measured in several regions of the rat central nervous system at different stages of postnatal development. For this, we have employed a combination of HPLC separation and radioimmunoassay detection using a neurokinin A antiserum which also recognizes neurokinin B and neuropeptide K. All 3 tachykinins were detectable during postnatal development in the various regions studied (hypothalamus, striatum, substantia nigra, cerebral cortex and spinal cord). Interestingly, a general increase in the tachykinin concentrations was observed during the second week of life. Some of these concentrations reached values on postnatal day 15 which far exceeded those observed in the adult. After day 15 most areas showed a slow decline in their tachykinin content until adult values were finally achieved. The developmental profiles obtained for these tachykinins are in good agreement with previous studies on the ontogeny of substance P and its receptors and support the view that tachykinins may play an important role in the organization and maturation of the developing central nervous system.     

The structure-function organization of neurokinin A and neurokinin B molecules. II. Theoretical conformational analysis of neurokinin B

The spatial structure of a neurokinin B molecule was investigated by the method of theoretical conformational analysis. The conformational analysis of this molecule indicated that the possible structure of neurokinin B under polar conditions may be described by five families of low-energy conformations possessing a conformationally relatively rigid C-terminal heptapeptide and variable N-terminal fragments.     

Neurokinin A and neurokinin B in the human retina

Very recently, the authors found levels of neurokinin (NK) A-like immunoreactivities in the human retina which were more than five times higher than those of substance P (SP). The present study aimed to find out how many of these immunoreactivities can be attributed to NKA and NKB and then the exact distribution pattern of both NKA and NKB was evaluated in the human retina and compared with that of SP. For this purpose, NKA-like immunoreactivities were characterized in the human retina by reversed phase HPLC followed by radioimmunoassay using the K12 antibody which recognizes both NKA and NKB. Furthermore, the retinae from both a 22- and 70-year-old donor were processed for double-immunofluorescence NKA/SP and NKB/SP. The results showed that NKA contributes to approximately two thirds and NKB to approximately one third of the immunoreactivities measured with the K12 antibody. NKA was found to be localized in sparse amacrine cells in the proximal inner nuclear layer, in displaced amacrine cells in the ganglion cell layer with processes ramifying in stratum 3 of the inner plexiform layer and also in sparse ganglion cells. By contrast, staining for NKB was only observed in ganglion cells and in the nerve fiber layer. Double-immunofluorescence revealed cellular colocalization of NKA with SP and also of NKB with SP. Thus, the levels of NKA and NKB are more than three and two times higher than those of SP, respectively. Whereas the distribution pattern of NKA is typical for neuropeptides, the localization of NKB exclusively in ganglion cells is atypical and unique.     

Structure-function organization of neurokinin A and neurokinin B molecules. I. Theoretical conformational analysis of neurokinin A

The spatial structure of the neurokinin A molecule was studied by the method of theoretical conformational analysis. On the basis of fragmental analysis, stable structures of the neurokinin A molecule under polar conditions were determined. The structures can be described by four families of low-energy conformations having a relatively labile tripeptide at the C-end and a conformationally rigid heptapeptide at the N-end. It was shown that two of these conformations are virtually isoenergetic structures. One of these is an alpha-helical structure and the other forms two beta-turns at the N-terminus, which change to the turn of the alpha-helix at the C-end.     

Structure-function organization of neurokinin A and neurokinin B molecules. III. A conformational study of glycine-monosubstituted analogues of neurokinins A and B

The conformational features of some glycine-monosubstituted analogues of neurokinins A and B were investigated by the method of theoretical conformational analysis. The calculated geometry and energy parameters permitted one to determine the structural role of each of these substituted amino acids in the mechanism of folding of the low-energy conformational states of neuropeptides. On the basis of the calculated data and the results of biological tests of these analogues, the structure-function relationships of neurokinins A and B were discussed.     

A regulatory role for neurokinin B in placental physiology and pre-eclampsia

Tachykinin dogma has assumed, so far, that neurokinin B (NKB) is a neuropeptide that is not produced in any peripheral tissue even though its endogenous receptor, NK3, has been found in a number of locations throughout the human body. We have found an abundant source of peripheral NKB in the human and rat placenta. In this review we describe the discovery of NKB in the placenta and examine its possible role in placental physiology and pre-eclampsia (PE). Excessive secretion of placental NKB into the maternal circulation during the third trimester of pregnancy has been found in women suffering from PE. This may provide the key to the cause of the multiple and complex symptoms associated with this potentially life-threatening illness. We also reveal the structural organisation of the human NKB gene for the first time as well as discussing putative mechanisms for its control.     

Effect of water trough type on the drinking behaviour of pasture-based beef heifers

The objective of this study was to investigate the effects of different trough types on the water consumption and drinking behaviour of pasture-based beef heifers. Two trials were implemented with 32 beef heifers to test two different types of water troughs, namely a rectangular concrete trough (RC) and a round polyvinyl chloride water tank (PVC). In Trial 1, both troughs were simultaneously available to groups of four animals within eight paddocks. In Trial 2, the animals were distributed in pairs throughout 16 paddocks and, in a crossover design, were exposed to one type of trough at a time. In both trials, estimated water intake was per four animals. Number of drinking bouts, time spent drinking and amount of water intake from the RC and PVC trough were recorded in both trials. Data were statistically analysed by analysis of variance. In Trial 1, group and trough effect were in the model. In Trial 2, stage, pair and trough were tested. In Trial 1, where both types of troughs were available, animals had a higher number of drinking bouts (3.32 v. 0.57 ± 0.09; P < 0.01), longer drinking periods (144.21 v. 22.81 ± 7.3 s; P < 0.01) and greater intake (160.21 v. 23.76 ± 13.06 l; P < 0.01) from the PVC water tank, compared to the RC trough. In Trial 2, all groups drank more often (5.10 v. 3.28 ± 0.32; P < 0.001), for longer periods (167.23 v. 115.23 ± 15.61 s; P < 0.02) and with higher intake (141.36 v. 118.47 ± 5.01 l; P < 0.02) from the PVC than from the RC trough. Thus, heifers not only prefer, but also drink more from a PVC water tank in comparison to a RC trough.     

Effect of neurokinin A on human temporal muscle blood flow

The effect of neurokinin A on human temporal muscle blood flow was compared to saline when injected into the muscle in six normal subjects. The 133-Xenon washout technique was used and the test solutions administered in a double-blind, cross-over manner. Neurokinin A (0.02 ml, 10(-5)M) caused a blood flow increase of 193%, while saline caused an increase of 23%. The difference between neurokinin A and saline was significant (p less than 0.05). It is suggested that a possible pathophysiological role of neurokinin A in migraine must involve modulation of vascular response as well as of primary nociception.     

Effect of hunger on the drinking behaviour of rodents adapted for mesic and xeric environments

Observations of drinking behaviour were taken on six rodent species during fasting. Four of these species were wild-caught and had not previously been examined for food deprivation polydipsia (FDP). These data support an hypothesis that a negative correlation exists between water availability in the natural habitat and the occurrence of FDP. Namely, xerophilous species exhibit an absolute polydipsia during food deprivation while mesically adapted species evidence depressed water consumption. Urine analyses during food deprivation indicated substantial decreases in electrolyte and osmotic pressure concentrations in all species. The drinking patterns of the three desert species investigated are discussed with reference to the availability of green vegetation in the natural habitat; however, there is presently no explanation for the observed polydipsia.     

Modelling the effect of immigration on drinking behaviour

A drinking model with immigration is constructed. For the model with problem drinking immigration, the model admits only one problem drinking equilibrium. For the model without problem drinking immigration, the model has two equilibria, one is problem drinking-free equilibrium and the other is problem drinking equilibrium. By employing the method of Lyapunov function, stability of all kinds of equilibria is obtained. Numerical simulations are also provided to illustrate our analytical results. Our results show that alcohol immigrants increase the difficulty of the temperance work of the region.     

Relative bronchoconstrictor activity of neurokinin A and neurokinin A fragments in guinea pigs.

We examined the effect of rapid intravenous infusion of neurokinin A (NKA) and selected COOH-terminal NKA fragments on pulmonary conductance (GL) and dynamic compliance in anesthetized mechanically ventilated guinea pigs. The rank order of the dose of peptide required to reduce GL by 50% (ED50GL) was NKA = NKA2-10 = NKA3-10 = NKA4-10 less than NKA5-10 much less than NKA6-10. The time course of bronchoconstriction induced by NKA2-10, NKA3-10, and NKA4-10 was similar to that induced by NKA, whereas NKA5-10 and NKA6-10 each had a shorter duration of action than NKA for a similar induced maximal change in GL. To determine whether degradation of these NKA fragments by neutral endopeptidase (NEP) modulates their bronchoconstrictor activity as it does for native NKA, we examined the effect of the NEP inhibitor SCH32615 on NKA3-10-, NKA5-10-, and NKA6-10-induced changes in GL. We have previously reported that the ED50GL for NKA was approximately 20-fold lower in animals pretreated with SCH32615 (1 mg/kg) than in control guinea pigs. SCH32615 caused a 16-fold decrease in ED50GL for NKA3-10 (P less than 0.001) but had no effect on airway responses to NKA5-10 or NKA6-10. The results demonstrate that the magnitude and duration of bronchoconstriction induced by potential aminopeptidase degradation products of NKA are similar to those of the native peptide. Aminopeptidases do not, therefore, have the capacity to modulate the bronchoconstriction induced by this peptide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Substance P, neurokinin A, and neurokinin B induce generation of IL-1-like activity in P388D1 cells. Possible relevance to arthritic disease

Near nanomolar concentrations of substance P induce production of IL-1 or an IL-1-like activity in the mouse macrophage cell line P388D1. Moreover, this could be accomplished with the carboxyl-terminal octapeptide substance P4-11, and could be inhibited with the substance P antagonist [D-Pro2, D-Trp7,9]-substance P. Two other mammalian neurokinins, neurokinin A and neurokinin B, were also found to induce secretion of IL-1-like activity in P388D1 cells. These findings suggest that activation of immune cells by neuromodulators can contribute to the maintenance of the chronic inflammatory state and the immunopathology observed in arthritic disease mediated by IL-1. The results also suggest that one approach to the treatment of rheumatoid arthritis might be to attempt to inhibit the local effects of immuno-modulatory neuropeptides, specifically the neurokinins, in affected joints.     

Structure-activity studies of heptapeptide derivatives related to substance P, neurokinin A, B and other tachykinins on smooth muscles

Diverse C-terminal heptapeptide derivatives related to substance P, kassinin, physalaemin, neurokinin A and B were synthesized and the contracting activities on the guinea pig ileum as well as rat duodenum were compared. In the partial sequence of C-terminal of tachykinin peptides, -I-II-Phe-III-Gly-Leu-Met-NH2, the combination of amino acid residues at positions I and III have significant roles in contraction of smooth muscle. For the activation of rat duodenal muscle (SP-E), Asp(I) and aliphatic amino acid(III), and for guinea pig ileal muscle(SP-P), Gln(I) and aromatic amino acid(III) are essential. Moreover, guinea pig ileum is sensitive to a full sequence of neurokinin peptides.     

Neurokinin A, neurokinin B and neuropeptide K in the rabbit iris: a study comparing different extraction methods

Neurogenic inflammation in the rabbit eye is thought to be partly mediated by tachykinins released from trigeminal sensory nerve fibres. In the present study we have investigated the occurrence of neurokinin A (NKA), neurokinin B (NKB), neuropeptide K (NPK) and related immunoreactive components in the rabbit iris-ciliary complex using neutral and different types of acidic media for extraction, reverse phase high performance liquid chromatography (RP-HPLC) and radioimmunoassay (RIA). The immunoreactive material detected with an antiserum reacting almost equally well with NKA, NKB and NPK consisted mainly of NKA, and small amounts of NPK but almost no NKB. Acidic media seemed to be more effective than neutral media for extraction of NKA and NPK. Acid extraction yielded also an NKA-immunoreactive component which eluted immediately before NKA while neutral extracts, on the other hand, contained a component which appeared behind NKA, i.e. in the position of NKA-(3-10) and NKA-(4-10). The present results indicate that NKA but not NKB may play a role in neurogenic inflammation in the rabbit eye.     

Stereotyped behaviour,adjunctive drinking and the feeding periods of tethered sows

The behaviour of 25 tethered sows in an intensive piggery was observed for 1 h before and 1 h after the delivery of food to determine if behavioural stereotypies appeared as adjunctive behaviours. The different components of behavioural stereotypies were found to have different associations with the feeding period. Head-waving, bar-biting, and rubbing the snout against the cage were most common before feeding, and were shown particularly by the older sows. Manipulating the drinker and, for some sows, rubbing were most common after. There was some evidence of polydipsia. Vacuum chewing, playing with the chain, and aggressive behaviours, however, did not appear to be associated with the feeding period. The last two behaviours occurred only rarely. Seven sows showed stereotyped sequences of rapid rubbing or rapid drinking after the delivery of food, and these sows showed more excitement before food was delivered. Rooting was common for the full hour after all food had been consumed, and occurred in conjunction with long duration drinking. I suggest that the occurrence of adjunctive drinking by sows results from the persistence of feeding motivation, perhaps because concentrated food does not provide sufficient stomach distension, combined with the knowledge that food will definitely not be forthcoming. Stereotyped sequences of behaviour may be a means of reducing the arousal generated by the expectation of food.