Tachykinins belong to a large, evolutionarily conserved family of brain/gut peptides that are involved in a variety of physiological functions in mammals, such as reproductive regulation. However, little information was available about tachykinins in ancient fish lineage. In the present study, we firstly identified three tachykinin genes (named tac1, tac3 and tac4) and three neurokinin receptors (named nk1r, nk2r and nk3r) from Chinese sturgeon brain and pituitary. Sequence analysis showed that tac1 encoded substance P (SP) and neurokinin A (NKA), tac3 encoded neurokinin B (NKB) and NKB-related peptide (NKBRP), and tac4 encoded hemokin 1 (HK-1) and hemokin 2 (HK-2), respectively. The luciferase reporter assay results showed that NK1R preferentially selected asSP, NK2R preferentially selected asNKA, and NK3R preferentially selected asNKB. Tissue expression analysis showed that the three tac genes were highly detected in the telencephalon and hypothalamus, whereas nkr genes were widely expressed in peripheral tissues. Spatio-temporal expression analysis showed that all three tac genes were highly expressed in unknown sex individuals. Intraperitoneal injection experiments showed that both asSP and asNKB could stimulate luteinizing hormone (LH) release in Chinese sturgeon serum. At the transcriptional level, asSP and asNKB could significantly reduce pituitary follicle-stimulating hormone beta (fshβ) mRNA expression, but induce pituitary growth hormone (gh) mRNA expression. In addition, estradiol (E2) could stimulate tac3 mRNA expression in hypothalamus. Taken together, this study provided information on the tachykinin family in Chinese sturgeon and demonstrates that asNKB and asSP could be involved in reproductive and growth regulation in pituitary.

01 Jun 2023·The International Journal of Lower Extremity Wounds

Substance P, a Neuropeptide, Promotes Wound Healing via Neurokinin-1 Receptor

Article

Author: Kumar, Dinesh ; Mahapatra, Puspendra S. ; Gopalakrishnan, Anu ; Gupta, Vijayta ; Kant, Vinay ; Bag, Sadhan ; Kumar, Dhirendra

Substance P (SP), an endogenous neuropeptide, mediates intracellular signaling, mainly through a tachykinin receptor. The tachykinin receptors family consists of neurokinin-1 (NK-1), neurokinin-2 (NK-2), and neurokinin-3 receptors. Our previous studies on SP have shown its wound healing potentials. But the exact mechanism of wound healing by SP is not exactly known. In view of this, the present study was aimed at evaluating the in vitro wound healing effect of SP alone and in the presence of NK-1, NK-2, and both receptor antagonists. Scratch assay, transwell assay, and tumor growth factor-beta 1 (TGF-β1) assay were performed on buffalo fetal fibroblast culture. The cotreatment of fibroblast cultures with SP alone during the 24 h caused the significant proliferation and migrations of cells in both horizontal and vertical directions. The SP in the presence of spantide II (NK-1 antagonist) failed to stimulate this migration. The treatment of cells with SP in the presence of NK-2 antagonist treatment also showed a significant reduction of migration of cells with respect to SP treatment alone. The SP in the presence of both NK-1 and NK-2 antagonists failed to stimulate the horizontal migration of cells and most of the ineffectiveness of SP was observed in this combination. The TGF-β1 levels were significantly higher in the supernatants of cells that were exposed to SP alone. All other treatments have significantly lower TGF-β1 levels than SP alone treatment. It is concluded that different actions on fibroblast cells by SP were mainly mediated through the NK-1 receptor.

01 Jan 2023·Reproductive Sciences

Female Infertility Is Associated with an Altered Expression Profile of Different Members of the Tachykinin Family in Human Granulosa Cells

Article

Author: Fernández-Sánchez, Manuel ; Fernández-Atucha, Ainhoa ; Dodd, Nicolás Prados ; Candenas, Luz ; Blasco, Víctor ; Pinto, Francisco M

Neurokinin B (NKB) and its cognate receptor, NK3R, play a key role in the regulation of reproduction. NKB belongs to the family of tachykinins, which also includes substance P and neurokinin A, both encoded by the by the gene TAC1, and hemokinin-1, encoded by the TAC4 gene. In addition to NK3R, tachykinin effects are mediated by NK1R and NK2R, encoded by the genes TACR1 and TACR2, respectively. The role of these other tachykinins and receptors in the regulation of women infertility is mainly unknown. We have analyzed the expression profile of TAC1, TAC4, TACR1, and TACR2 in mural granulosa and cumulus cells from women presenting different infertility etiologies, including polycystic ovarian syndrome, advanced maternal age, low ovarian response, and endometriosis. We also studied the expression of MME, the gene encoding neprilysin, the most important enzyme involved in tachykinin degradation. Our data show that TAC1, TAC4, TACR1, TACR2, and MME expression is dysregulated in a different manner depending on the etiology of women infertility. The abnormal expression of these tachykinins and their receptors might be involved in the decreased fertility of these patients, offering a new insight regarding the diagnosis and treatment of women infertility.

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