Sophorolipid Biosurfactants Activate Taste Receptor Type 1 Member 3‐Mediated Taste Responses and Block Responses to Bitter Taste In Vitro and In Vivo

2019 ◽  
Vol 22 (3) ◽  
pp. 441-449 ◽  
Author(s):  
Mehmet Hakan Ozdener ◽  
Richard D. Ashby ◽  
Masafumi Jyotaki ◽  
Nadia Elkaddi ◽  
Andrew I. Spielman ◽  
...  
Keyword(s):  
Bitter Taste ◽  
Taste Receptor ◽  
Receptor Type

scholarly journals Cannabinoid Receptor Type 1 Regulates Drug Reward Behavior via Glutamate Decarboxylase 67 Transcription

2021 ◽  
Vol 22 (19) ◽  
pp. 10486
Author(s):  
Sun Mi Gu ◽  
Sowoon Seo ◽  
Daejin Park ◽  
Sanghyeon Kim ◽  
Santosh Lamichhane ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Glutamate Decarboxylase ◽  
Cannabinoid Receptor ◽  
Mrna Level ◽  
Receptor Type ◽  
Striatal Slices ◽  
Cannabinoid Receptor Type 1

Interaction of cannabinoid receptor type 1 (CB1) and GABAergic neuronal activity is involved in drug abuse-related behavior. However, its role in drug-dependent Pavlovian conditioning is not well understood. In this study, we aimed to evaluate the effects of a CB1 agonist, JWH-210, on the development of conditioned place preference (CPP)-induced by methamphetamine (METH). Pretreatment with a synthetic cannabinoid, JWH-210 (CB1 agonist), increased METH-induced CPP score and METH-induced dopamine release in acute striatal slices. Interestingly, CB1 was expressed in glutamate decarboxylase 67 (GAD67) positive cells, and overexpression of CB1 increased GAD67 expression, while CB1 knockdown reduced GAD67 expression in vivo and in vitro. GAD67 is known as an enzyme involved in the synthesis of GABA. CB1 knockdown in the mice striatum increased METH-induced CPP. When GAD67 decreased in the mice striatum, mRNA level of CB1 did not change, suggesting that CB1 can regulate GAD67 expression. GAD67 knockdown in the mouse striatum augmented apomorphine (dopamine receptor D2 agonist)–induced climbing behavior and METH-induced CPP score. Moreover, in the human brain, mRNA level of GAD67 was found to be decreased in drug users. Therefore, we suggest that CB1 potentiates METH-induced CPP through inhibitory GABAergic regulation of dopaminergic neuronal activity.

scholarly journals Human complement receptor type 1–directed loading of tissue plasminogen activator on circulating erythrocytes for prophylactic fibrinolysis

Blood ◽  
2006 ◽  
Vol 108 (6) ◽  
pp. 1895-1902 ◽  
Author(s):  
Sergei Zaitsev ◽  
Kristina Danielyan ◽  
Juan-Carlos Murciano ◽  
Kumkum Ganguly ◽  
Tatiana Krasik ◽  
...  
Keyword(s):  
Receptor Type ◽  
Tissue Type ◽  
Clot Lysis ◽  
Complement Receptor ◽  
Complement Receptor Type ◽  
Human Rbcs ◽  
Complement Receptor Type 1

AbstractPlasminogen activators (PAs) are not used for thromboprophylaxis due to rapid clearance, bleeding, and extravascular toxicity. We describe a novel strategy that overcomes these limitations. We conjugated tissue-type PA (tPA) to a monoclonal antibody (mAb) against complement receptor type 1 (CR1) expressed primarily on human RBCs. Anti-CR1/tPA conjugate, but not control conjugate (mIgG/tPA), bound to human RBCs (1.2 × 103 tPA molecules/cell at saturation), endowing them with fibrinolytic activity. In vitro, RBC-bound anti-CR1/tPA caused 90% clot lysis versus 20% by naive RBCs. In vivo, more than 40% of anti-CR1/125I-tPA remained within the circulation (∼90% bound to RBCs) 3 hours after injection in transgenic mice expressing human CR1 (TgN-hCR1) versus less than 10% in wild-type (WT) mice, without RBC damage; approximately 90% of mIgG/125I-tPA was cleared from the circulation within 30 minutes in both WT and TgN-hCR1 mice. Anti-CR1/tPA accelerated lysis of pulmonary emboli and prevented stable occlusive carotid arterial thrombi from forming after injection in TgN-hCR1 mice, but not in WT mice, whereas soluble tPA and mIgG/tPA were ineffective. Anti-CR1/tPA caused 20-fold less rebleeding in TgN-hCR1 mice than the same dose of tPA. CR1-directed immunotargeting of PAs to circulating RBCs provides a safe and practical means to deliver fibrinolytics for thromboprophylaxis in settings characterized by a high imminent risk of thrombosis.

scholarly journals A Balance Theory of Peripheral Corticotropin-Releasing Factor Receptor Type 1 and Type 2 Signaling to Induce Colonic Contractions and Visceral Hyperalgesia in Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (12) ◽  
pp. 4655-4664 ◽  
Author(s):  
Tsukasa Nozu ◽  
Kaoru Takakusaki ◽  
Toshikatsu Okumura
Keyword(s):  
Colonic Motility ◽  
Corticotropin Releasing Factor ◽  
Receptor Type ◽  
In Vivo Studies ◽  
Induced Response ◽  
Visceral Hyperalgesia ◽  
Visceromotor Response

Several recent studies suggest that peripheral corticotropin-releasing factor (CRF) receptor type 1 (CRF1) and CRF2 have a counter regulatory action on gastrointestinal functions. We hypothesized that the activity balance of each CRF subtype signaling may determine the changes in colonic motility and visceral sensation. Colonic contractions were assessed by the perfused manometry, and contractions of colonic muscle strips were measured in vitro in rats. Visceromotor response was determined by measuring contractions of abdominal muscle in response to colorectal distensions (CRDs) (60 mm Hg for 10 min twice with a 30-min rest). All drugs were administered through ip route in in vivo studies. CRF increased colonic contractions. Pretreatment with astressin, a nonselective CRF antagonist, blocked the CRF-induced response, but astressin2-B, a selective CRF2 antagonist, enhanced the response by CRF. Cortagine, a selective CRF1 agonist, increased colonic contractions. In in vitro study, CRF increased contractions of muscle strips. Urocortin 2, a selective CRF2 agonist, itself did not alter the contractions but blocked this increased response by CRF. Visceromotor response to the second CRD was significantly higher than that of the first. Astressin blocked this CRD-induced sensitization, but astressin2-B or CRF did not affect it. Meanwhile, astressin2-B together with CRF significantly enhanced the sensitization. Urocortin 2 blocked, but cortagine significantly enhanced, the sensitization. These results indicated that peripheral CRF1 signaling enhanced colonic contractility and induced visceral sensitization, and these responses were modulated by peripheral CRF2 signaling. The activity balance of each subtype signaling may determine the colonic functions in response to stress.

scholarly journals Longitudinal Expression of Testicular TAS1R3 from Prepuberty to Sexual Maturity in Congjiang Xiang Pigs

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 437
Author(s):  
Ting Gong ◽  
Weiyong Wang ◽  
Houqiang Xu ◽  
Yi Yang ◽  
Xiang Chen ◽  
...  
Keyword(s):  
Sexual Maturity ◽  
Cell Function ◽  
Expression Patterns ◽  
Taste Receptor ◽  
Receptor Type ◽  
Mrna Levels ◽  
Early Puberty ◽  
Specific Expression

Testicular expression of taste receptor type 1 subunit 3 (T1R3), a sweet/umami taste receptor, has been implicated in spermatogenesis and steroidogenesis in mice. We explored the role of testicular T1R3 in porcine postnatal development using the Congjiang Xiang pig, a rare Chinese miniature pig breed. Based on testicular weights, morphology, and testosterone levels, four key developmental stages were identified in the pig at postnatal days 15–180 (prepuberty: 30 day; early puberty: 60 day; late puberty: 90 day; sexual maturity: 120 day). During development, testicular T1R3 exhibited stage-dependent and cell-specific expression patterns. In particular, T1R3 levels increased significantly from prepuberty to puberty (p < 0.05), and expression remained high until sexual maturity (p < 0.05), similar to results for phospholipase Cβ2 (PLCβ2). The strong expressions of T1R3/PLCβ2 were observed at the cytoplasm of elongating/elongated spermatids and Leydig cells. In the eight-stage cycle of the seminiferous epithelium in pigs, T1R3/PLCβ2 levels were higher in the spermatogenic epithelium at stages II–VI than at the other stages, and the strong expressions were detected in elongating/elongated spermatids and residual bodies. The message RNA (mRNA) levels of taste receptor type 1 subunit 1 (T1R1) in the testis showed a similar trend to levels of T1R3. These data indicate a possible role of T1R3 in the regulation of spermatid differentiation and Leydig cell function.

scholarly journals Effect of Coxsackievirus B4 Infection on the Thymus: Elucidating Its Role in the Pathogenesis of Type 1 Diabetes

2021 ◽  
Vol 9 (6) ◽  
pp. 1177
Author(s):  
Abdulaziz Alhazmi ◽  
Magloire Pandoua Nekoua ◽  
Hélène Michaux ◽  
Famara Sane ◽  
Aymen Halouani ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Viral Infections ◽  
Lymphoid Organ ◽  
Thymic Epithelial Cells ◽  
Central Tolerance ◽  
Coxsackievirus B4

The thymus gland is a primary lymphoid organ for T-cell development. Various viral infections can result in disturbance of thymic functions. Medullary thymic epithelial cells (mTECs) are important for the negative selection of self-reactive T-cells to ensure central tolerance. Insulin-like growth factor 2 (IGF2) is the dominant self-peptide of the insulin family expressed in mTECs and plays a crucial role in the intra-thymic programing of central tolerance to insulin-secreting islet β-cells. Coxsackievirus B4 (CVB4) can infect and persist in the thymus of humans and mice, thus hampering the T-cell maturation and differentiation process. The modulation of IGF2 expression and protein synthesis during a CVB4 infection has been observed in vitro and in vivo in mouse models. The effect of CVB4 infections on human and mouse fetal thymus has been studied in vitro. Moreover, following the inoculation of CVB4 in pregnant mice, the thymic function in the fetus and offspring was disturbed. A defect in the intra-thymic expression of self-peptides by mTECs may be triggered by CVB4. The effects of viral infections, especially CVB4 infection, on thymic cells and functions and their possible role in the pathogenesis of type 1 diabetes (T1D) are presented.

Sophorolipid Reduces Bitter Taste in Humans In Vivo and In Vitro

2021 ◽  
Author(s):  
Mehmet Hakan Ozdener ◽  
Andrew I. Spielman ◽  
Paul M. Wise
Keyword(s):  
Bitter Taste
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