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Neurokinin B (NKB) is a hypothalamic neuropeptide containing 10 amino acids and is an essential member of the tachykinin family. Based on studies in mammals, Kiss, NKB, and dynorphin A are located in the common neurons, named KNDy neurons, and NKB and Kiss can stimulate the GnRH pulses. In humans, the mutations of NKB and its receptor NK3R can lead to hypogonadotropic hypogonadism and infertility. NKB is also involved in many other physiological activities in mammals and has received increasing attention. NKB was first purified from porcine spinal cord extracts and named neurokinin B or neuromedin K. Subsequently, NKB has been identified in various species, and its encoding gene was named tac2 in ruminants and rodents, and tac3 in other mammals, birds, reptiles, amphibians, and fish. In teleosts, the NKB system was first identified in zebrafish by three laboratories in 2012; it was also found in grass carp, goldfish, Nile tilapia, European eel, orange-spotted grouper, and half-smooth tongue.As teleosts have experienced the third round of genome duplication (3R), the bony fish have two forms of tac3 genes, namely tac3a and tac3b. However, only tac3a is present in highly evolved fish species, such as Nile tilapia and orange-spotted grouper, whereas the tac3b gene has been lost. tac3 in fish and amphibians can encode two mature peptides, NKB and an NKB-related peptide (NKBRP), whereas there is only NKB in mammals, birds, and reptiles. NKB and NKBRP sequences are highly conserved, and sequence analysis showed that NKB and NKBRP share an identical -FXGLM motif at the C-terminus, and X is a hydrophobic or aromatic amino acid residue, which plays an important role in binding to homologous receptors.NKB exerts biological effects by activating the endogenous receptor NK3R. The NK3R receptor belongs to the G protein-coupled receptor family and has a typical seven-transmembrane structure. NK3R is encoded by the tacr3 gene. There are two tacr3 subtypes in teleosts: tacr3a and tacr3b. There was an additional gene, called tacr3a2, in the zebrafish and grass carp, and it was produced by local genome duplication of tacr3a1. The tissue distribution shows that tac3 and tacr3 are widely expressed in the central nervous system and peripheral tissues, indicating that they have essential physiological functions. The specific expression patterns vary depending on the species. They are mainly expressed in the brain, with high expression levels in the pituitary, intestine, and gonads. NKB may participate in regulating reproduction and feeding in teleosts.Currently, studies in teleosts mainly focus on reproductive and feeding regulation. Due to the existence of multiple forms of tac3 and tacr3 genes in teleosts, the action of the NKB system on reproduction control is more complex. Using different experiment methods, such as intraperitoneal injection, intramuscular injection, and incubation of pituitary cells or pituitaries, NKB affected the expression of gnrh, kiss, lhβ, and fshβ and the secretion of LH, FSH, and E2 in fish. The physiological effects varied depending on the gonadal development stages, species, sex, treatment methods, treatment time, and dose. In addition, NKB can act as an anorectic peptide to inhibit food intake and promote gastrointestinal motility. It could also affect the expression of growth-related genes. In summary, as a neurotransmitter or neuromodulator in the central nervous system and a major member of the brain-gut peptides, the NKB system plays an important role in teleosts.Tachykinins activate receptors by coupling to Gαs and Gαq proteins, transducing its signals via PKA and PKC pathways. NKB and NKBRP could activate the PKA/PKC pathway via cognate receptors in some teleosts. This could be verified because different pathway inhibitors could block the effects of NKB and NKBRP. Upon binding to NK3R, NKB induces the secretion of related neuropeptides and the expression of related genes through the AC/cAMP/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMK-Ⅱ cascades. The C-terminal motif of NKB is crucial to binding receptors; once it is changed, NKB cannot activate the downstream signaling of NK3R, indicating that the integrity of the NKB/NK3R system is essential for the normal functioning of NKB. There are many deficiencies in the research regarding the function of NKB in teleosts. The specific effects and mechanisms of regulating reproductive endocrinology remain unclear, and the functional and signaling interactions between NKB and other neuroendocrine factors such as Kiss, GnIH, and GnRH require further study. In addition, the physiological functions of NKB in fish are mainly focused on reproductive regulation, with less attention given to feeding regulation and other physiological effects.In conclusion, this review provides a summary of the research progress on the NKB system in teleosts, including the identification, tissue distribution, physiological functions, and signaling mechanisms of NKB and its receptors, to enhance the understanding of the NKB system in fish and provide a reference for future research.

Sea-land relay transportation (SRT) is a key part of the “land-based greenhouse + offshore net cage” mariculture system for yellowtail kingfish. In this study, the physiological status of yellowtail kingfish during SRT was assessed by determining serum biochemical indexes (levels of cortisol, glucose, and malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and catalase (CAT)), the composition of intestinal microflora, and the liver transcriptome before (control), during, and after transportation (T1 and T2) and after recovery for 6 hours (6 h), 12 hours (12 h), 1 day (D1), 3 days (D3), and 7 days (D7). The results show that the serum cortisol and glucose levels, MDA level, and activities of SOD and CAT significantly increased during transportation, and decreased to similar levels to those in the control after 1 day of recovery. Bacteria including Acinetobacter, Enterobacter, and Comamonas accounted for more than 91 % of the microbial community in the gut of yellowtail kingfish, and these genera were associated with changes in serum glucose levels, indicating that they may help to alleviate the effects of transportation stress. Analyses of liver transcriptome data showed that significantly differentially expressed genes (DEGs) in the T2, D1, D3 and D7 groups were significantly enriched in the “Protein processing in the endoplasmic reticulum (ER)” pathway. At the end of transportation (T2 group), the ER-associated degradation (ERAD) pathway was activated, with up-regulation of hsp40, hsp70, and hsp90α. The transcript levels of these genes gradually returned to levels similar to those in the control during the recovery period. At the first day of recovery, the unfolded protein response imposed stress upon the ER, accompanied by significant down-regulation of PEPK and Calmin and significant up-regulation of CRT. The DEGs in the D3 group were enriched in the “ER”, “Steroid biosynthesis”, “Fatty acid degradation”, “PPAR signaling”, and “Fat digestion and absorption” pathways, whereas the number of DEGs related to lipid metabolism and stress pathways was significantly decreased in the D7 group. Our results indicate that hsp70 and hsp90α can be used as stress markers, and hsp40 can be used as a physio-metabolic recovery marker for yellowtail kingfish. These results show that, although serum indices recovered 24 hours after transportation, up to 3 days after transportation is an important period for recovery from transportation stress at the transcriptome level. “Protein processing in the ER pathway” is an important pathway regulating stress and recovery in yellowtail kingfish.

The neurokinin B (NKB) system acts as a crucial modulator in the regulation of reproduction and feeding in mammals, however limited information is available in teleosts regarding its potential role in reproductive functions. Herein, we have identified its encoding gene, namely tachykinin 3 (tac3), in the yellowtail kingfish. The full-length tac3 cDNA sequence was 372 bp in size and encoded a 123-aa preprohormone, including two mature peptides, NKB and NKF. Tissue distribution analysis showed that tac3 was primarily expressed in the intestine of yellowtail kingfish. During embryonic development, the highest mRNA levels of tac3 were observed at stage 4 (16-cell) and stage 14 (newly-hatched larva). The peak of tac3 transcript levels was also noticed at 30 days post-hatching during early ontogeny. The physiological effects of NKB and NKF on expression of brain and pituitary genes along with plasma hormones levels were further analyzed by intraperitoneal injection. NKB exerted a stimulatory effect on gnrh1, gnrh2, gnih, and kiss2r mRNA levels, but suppressed kiss1r, gnihr, gal, gh, lhβ, and fshβ mRNA levels. An evident increase was observed on transcript levels of gnrh1, gnrh2, kiss1, kiss2, gnih, and gnihr after NKF treatment, whereas kiss1r, kiss2r, gh, lhβ, and fshβ mRNA levels were down-regulated. Moreover, NKF, but not NKB, reduced serum estradiol levels, and both of these two peptides suppressed serum 11-keto testosterone levels. Taken together, our results provide preliminary evidence that the NKB system participates in the control of reproduction in yellowtail kingfish via acting on brain, pituitary and gonadal hormones.