Background: The cumulus cells (CC) play an essential role in protecting oocytes and providing molecular signals for meiotic and cytoplasmic maturation. Gonadotropins stimulate CC proliferation, promote the release of factors that resume oocyte maturation, and activate small G proteins. Among these, Ras, a GTP-binding protein, participates in signaling pathways that regulate cell growth, division, and proliferation. This study aimed to investigate the changes in the Ras subfamily and gonadotropin receptor expression during porcine CC maturation. Methods: Cumulus-oocyte complexes (COCs) were incubated in a medium supplemented with follicular stimulating hormone (FSH), luteinizing hormone (LH), and epidermal growth factor (EGF) for 44 hours. CCs were collected from the COCs at 0, 22, and 44 hours, and mRNA expression levels of gonadotropin and growth factor receptors (FSHR, LHR, EGFR), Ras subfamily members (H-Ras, K-Ras, N-Ras, R-Ras), and Ras GTPases (RASA1, SOS1) were analyzed using quantitative RT-PCR. Results: The results revealed that LHR and R-Ras mRNA expression significantly increased only at 44 hours compared to the 0-hour group (p < 0.05). Conversely, RASA1 mRNA levels decreased significantly at the same time points. No significant changes were observed in H-Ras, K-Ras, N-Ras , or SOS1 expression. Conclusions: In conclusion, the observed increase in LHR and R-Ras and the decrease in RASA1 provide new insights into the molecular dynamics of Ras subfamily members during porcine CC maturation, contributing to a better understanding of the regulatory mechanisms underlying oocyte development.

Sympathetic innervation stimulates β-adrenergic receptors, triggering cyclic adenosine monophosphate (cAMP) production and enhancing protein secretion in salivary gland cells. While cAMP signaling, in conjunction with Ca2+ signaling, is essential for salivary gland function, the identified cAMP-producing G-protein-coupled receptors (GPCRs) remains limited. Here, we report the presence of cAMP-producing adenosine receptors in salivary gland cells. By reanalyzing publicly available single-cell transcriptome datasets of human and mouse submandibular glands, we identified mRNA expression of adenosine A1, A2A, A2B, and A3 receptors. Additionally, we confirmed that 5’-N-ethylcarboxamidoadenosine (NECA), an adenosine A2B receptor agonist, increases cAMP levels in human salivary gland cells, suggesting a physiological role for adenosine A2B receptors. Our findings enhance understanding of adenosine’s regulatory function in salivary glands and highlight new avenues for research on cAMPproducing adenosine receptors.

Human bitter taste-sensing type 2 receptors (hTAS2Rs) are expressed in various human tissues and may be associated with various cell signaling pathways, cell progression, and cell physiology in each tissue. hTAS2Rs can be a potential drug target because it is also expressed in some cancer cells. Xanthorrhizol (XNT) has various biological activities, such as anticancer, antimicrobial, anti-inflammatory, and antioxidant. XNT produces a bitter taste, but the specific hTAS2R activated is unknown, and the hTAS2R-mediated effect of XNT on cancer cells has not been studied. This study discovered the target receptor of XNT among 25 hTAS2Rs and confirmed the possibility of the hTAS2R-mediated inhibition of cancer cell proliferation. XNT activated only one receptor, hTAS2R38 (EC50=1.606±0.021 g/mL), and its activity was inhibited by probenecid, a hTAS2R38 antagonist. When HepG2 and MCF-7 cells were treated with XNT or phenylthiocarbamide (PTC), a known hTAS2R38 agonist, both chemicals inhibited cancer cell proliferation. XNT targets the human bitter taste receptor TAS2R38 and inhibits the proliferation of HepG2 and MCF-7 cells mediated by TAS2R38. This suggests that TAS2R38 may be a new target for disease treatment and a potential new factor for drug development.

Salt is crucial for survival, yet excessive intake of sodium chloride can have adverse effects. In the fruit fly, Drosophila melanogaster, internal taste organs located in the pharynx play a pivotal role in determining whether to accept or reject food. However, our understanding of how pharyngeal gustatory receptor neurons (GRNs) perceive high salt levels is still limited. In this study, we discovered that a specific member of the ionotropic receptor family, Ir60b, is selectively expressed in a pair of GRNs that respond to high salt concentrations. Through a two-way choice assay (DrosoX) to measure ingestion volume, we established that IR60b, along with two coreceptors, IR25a and IR76b, is necessary to deter excessive salt consumption. Interestingly, mutants lacking external taste organs but retaining internal taste organs in the pharynx showed significantly higher salt avoidance compared to flies missing all three IRs while still possessing all taste organs. These findings underscore the crucial role of IRs in pharyngeal GRNs in regulating the intake of high salt levels.

Mutations in the luteinizing hormone/chorionic gonadotropin receptors (LH/CGRs), representatives of the G protein-coupled receptor family, have been rapidly identified over the last 20 years. This review aims to compare and analyze the data reported the activating and inactivating mutations of the LH/CGRs between human, rat, equine and fish, specifically (Japanese eel Anguilla japonica). Insights obtained through detailed study of these naturally-occurring mutations provide a further update of structure-function relationship of these receptors. Specifically, we present a variety of data on eel LH/CGR. These results provide important information about LH/CGR function in fish and the regulation of mutations of the highly conserved amino acids in glycoprotein hormone receptors.

담즙산은 지방의 소화를 돕고 담즙의 배출을 용이하게 하는 역할을 하는 것으로 알려져 있었다. 하지만 여러 연구를 통해 담즙산에 대한 수용체가 존재하며 그 종류도 다양함을 알게 되었다. 담즙산 수용체는 담즙산 생리에 관여하는 것 외에도 에너지 대사, 염증 조절 등의 반응에 있어 인체 내에서 광범위하게 작용한다. GPBAR1과 S1PR2는 담즙산 수용체 중에서도 대표적인 G 단백질 결합수용체로서 담관세포에 많이 존재하며 세포의 증식 및 담즙 분비 등에 관여한다. 아울러 담관암의 진행과도 관련되어 있다는 연구가 발표되고 있어 향후 담관암 치료에 중요한 표적이 될 것으로 예상된다.

This study aimed to investigate whether neurotransmitter receptors in the nervous system were also expressed in oral keratinocytes. Expressions of various neurotransmitter receptor genes in immortalized mouse oral keratinocyte (IMOK) cells were examined by reverse transcriptase polymerase chain reaction. IMOK cells expressed calcitonin gene-related peptide (CGRP) receptor subunit genes Ramp1 and Ramp3 and glutamate receptor subunit genes Grina , Gria3 , Grin1 , Grin2a , and Grin2d . Moreover, IMOK cells expressed Adrb2 and Chrna5 that encode beta 2 adrenergic receptor and cholinergic receptor nicotinic alpha 5 for sympathetic and parasympathetic neurotransmitters, respectively. The expression of Bdkrb1 and Ptger4 , which encode receptors for bradykinin and prostaglandin E2 involved in inflammatory responses, was also observed at low levels. Expressions of Ramp1 and Grina in the mouse gingival epithelium were also confirmed by immunohistochemistry. When the function of neurotransmitter receptors expressed on IMOK cells was tested by intracellular calcium response, CGRP, glutamate, and cholinergic receptors did not respond to their agonists, but the bradykinin receptor responded to bradykinin. Collectively, oral keratinocytes express several neurotransmitter receptors, suggesting the potential regulation of oral epithelial homeostasis by the nervous system.

The CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor that regulates chemotaxis and effector functions of immune cells. It also serves as the major co-receptor for the entry of human immunodeficiency virus (HIV). Recently, CCR5 inhibitors have been developed and used for the treatment or prevention of HIV infections. Additionally, it has been identified that CCR5 controls bone homeostasis by regulating osteoclastogenesis and the communication between osteoblasts and osteoclasts. However, the effects of CCR5 inhibition on bone tissue in elderly patients are unknown. This study aimed to examine the bone phenotype of aged CCR5 knockout (KO) mice. Femoral and tibial bones were isolated from 12-month and 18-month old wild-type (WT) and CCR5 KO mice, and microcomputed tomography and histology analyses were performed. Twelve-month-old CCR5 KO mice exhibited a decreased trabecular bone mass and cortical bone thickness in both femoral and tibial bones compared with agematched WT mice. Eighteen-month-old mice also showed a decreased trabecular bone mass in femurs compared with control WT mice, but not in tibial bones. Unlike in 12-month-old mice, the cortical margin of femurs and tibias in 18-month-old mice were rough, likely because they were aggravated by the deficiency of CCR5. Overall, our data suggest that the deficiency of CCR5 with aging can cause severe bone loss. When CCR5 inhibitors or CCR5 inactivating technologies are used in elderly patients, a preventive strategy for bone loss should be considered.

Chronic hypoxia is a major cause that increases neonatal mortality in the perinatal period. Vascular endothelial growth factor (VEGF) and its receptors induced by hypoxia are increased blood vessel permeability in the developing central nervous system and characterized as a critical factor in angiogenesis and vasculogenesis. This study investigated the development of the rat cerebellum with expression of VEGF and its receptors under chronic hypoxia in compare with normoxia. In addition, this study can contribute to the understanding of the effect development in the postnatal cerebellum. Rat pups were divided into two groups, normoxia and hypoxia group. The cerebellum of 35-day-old rat was removed and prepared for immunofluorescent staining. After staining, the sections were observed under the fluorescent microscope and were taken the picture using the microscopic-digital camera system. Expression of VEGF and Flk-1 restricted only to Purkinje cells, but feline sarcoma virus-like tyrosine kinase-1 (Flt-1) did not express in all of cerebellar layers. Under chronic hypoxia, expression of VEGF and fetal liver kinase-1 (Flk-1) increased in Purkinje cells but no changes in case of Flt-1. These results suggest that the source of VEGF and Flk-1 is Purkinje cells in the cerebellum. And increase of VEGF and Flk-1 expression in the murine cerebellum results from adaptive responses to chronic hypoxia.

The lutropin/chorionicgonadotropin receptor (LHR) is a member of the rhodopsin-like subfamily of G protein-coupled receptors (GPCRs) that have been shown to mediate the internalization of its five (activation: three; inactivation: two) naturally occurring mutation. Gonadotropin receptors are members of the seven transmembrane (TM) receptor families. Several point mutations in TM II, III, V and VI have been identified in the luteinizing hormone receptor (LHR) gene, leading to constitutive activation and inactivation of the receptor. In eelLHR, we generated 3 types of constitutive activating mutations (M410T, L469R and D590Y) and 2 types of constitutive inactivating mutations (D383N and Y546F) to investigate how they work on hormone-receptor interaction. To assess the functional effects of 5 receptor mutations directly, wild-type (WT) and mutant receptors were transiently expressed in CHO-K1 cells. We evaluated the basal and cAMP stimulation by rec-LH hormone. The activity was shown to be a dose-dependent increase in cAMP production in LHR-WT expressing cells with an EC50 of 24.3 ng/ml and basal cAMP level of 2.6 nM. However, three activation mutants (D590Y, L469R and M410T) was most elevated the basal cAMP response at 12.8, 21.7 and 6.1 nM, respectively. In two inactivation mutants (D383N and Y546F) are very low in the basal cAMP activation. The EC50 was also considerably decreased to 42.3 ng/ml and 1181 ng/ml, respectively.