• Asian-Australasian Journal of Animal Sciences
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• v.16 no.12
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• pp.1701-1704
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• 2003

Melatonin regulates circadian rhythms and reproduction changes in seasonally reproductive mammals through binding to high-affinity, G-protein-coupled receptors. Small Tail Han sheep that has significant characteristics of high prolificacy and nonseasonal ovulatory activity is an excellent local sheep breed in P. R. China. The exon 2 of the ovine melatonin receptor 1a (MTNR1A) gene was amplified and a uniform fragment of 824 bp was obtained in 150 ewes of Small Tail Han sheep. The 824 bp PCR product was digested with restriction endonucleases Mnl I and Rsa I, and genetic polymorphism was detected by PCR-RFLP. Polymorphic Mnl I site was detected at base position 605 of the exon 2 of the MTNR1A gene. There were two kinds of genotypes in Small Tail Han sheep, AB (303 bp, 236 bp/67 bp) and BB (236 bp/67 bp, 236 bp/67 bp). The results indicated that genotype AA (303 bp, 303 bp) at Mnl I-RFLP site did not exist in non-seasonal estrous Small Tail Han sheep, which suggested that there was an association between genotype AA (303 bp, 303 bp) and reproductive seasonality in sheep. Polymorphic Rsa I site was detected at base position 604 of the exon 2 of the MTNR1A gene. Three kinds of genotypes were found in Small Tail Han sheep, AA (290 bp, 290 bp), AB (290 bp, 267 bp/23 bp) and BB (267 bp/23 bp, 267 bp/23 bp). Least squares means of litter size in the first parity and the second parity for genotype AA (290 bp, 290 bp) at Rsa I-RFLP site were 0.43 and 1.06 more than those for genotype AB (290 bp, 267 bp/23 bp) in Small Tail Han sheep.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.311-321
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• 1996

Both $M_1$ and $M_2$ muscarinic receptors contain a triplet of amino acid residues consisting of leucine (L), tyrosine (Y) and threonine (T) at C-terminus ends of the second putative transmembrane domains. This triplet is repeated as LYT-LYT in $M_2$ receptors at the interface between the second transmembrane domain and the first extracellular loop. Interestingly, however, it is repeated in a transposed fashion (LYT-TYL) in the sequence of $M_1$ receptors. In this work, we employed site-directed mutagenesis to investigate the possible significance of this unique sequence diversity for determining the distinct differential cellular function at the two receptor subtypes. Mutation of the LYTTYL sequence of $M_1$ receptors to the corresponding $M_2$ receptor LYTLYT sequence did not result in a significant change in the binding affinity of the agonist carbachol. The reverse mutation at the $M_2$ receptor also did not modify agonist affinity. Surprisingly, the LYTLYT $M_1$ receptor mutant demonstrated markedly enhanced coupling to activation of phospholipase C without a change in its coupling to increased cyclic AMP formation. There was also an enhanced receptor sensitivity in transducing elevation of intracellular $Ca^{2+}$. On the other hand, the reverse $LYTLYT{\rightarrow}LYTTYL$ mutation in the $M_2$ receptor did not alter its coupling to inhibition of adenylate cyclase, but slightly enhanced its coupling to stimulation of phosphoinositide (PI) hydrolysis. Our data suggest that the LYTTYL/LYTLYT sequence differences between $M_1$ and $M_2$ muscarinic receptors are not important for specifying ligand binding and coupling of various subtypes of muscarinic receptors to different cellular signaling pathways although they might play a role in the modulation of muscarinic reseptor coupling to PI hydrolysis.

• Animal cells and systems
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• v.13 no.2
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• pp.205-212
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• 2009

Known as a female hormone, estrogen, performs important functions, and the activities of the hormone are mediated via the estrogen receptor. The principal objective of the present study was to assess the effects of a estrogen receptor agonist in male reproductive organs. In this study, the estrogen receptor alpha agonist, PPT, was injected subcutaneously into adult male mice. The effects of PPT on the murine reproductive system were histologically assessed at 3,5, and 8 weeks after treatment. In the treatment group, reductions were observed in the weight of the body, testis and epididymis. Microscopic examination revealed a reduction in seminiferous tubular diameter in the testis, and epithelial cell height in the epididymis during the experiment. 8 weeks after treatment, spermatogenesis was not detected, nor was the lumen of the seminiferous tubules. In the fertility test, 1 week after PPT injection, the fertilizing ability of males was decreased, and on the 2nd and 3rd weeks, complete infertility was observed. In conclusion, the injection of high concentrations of PPT into adult males induced physiological changes, including infertility, and also induced morphological changes, including a reduction in the height of epithelial cells within the reproductive system.

• Biomolecules & Therapeutics
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• v.27 no.5
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• pp.435-441
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• 2019

The capsaicin receptor TRPV1 (transient receptor potential vanilloid 1) has been an object of intense interest for pharmacological development on account of its critical role in nociception. In the course of structure activity analysis, it has become apparent that TRPV1 ligands may vary dramatically in the rates at which they interact with TRPV1, presumably reflecting differences in their abilities to penetrate into the cell. Using a fast penetrating agonist together with an excess of a slower penetrating antagonist, we find that we can induce an agonist response of limited duration and, moreover, the duration of the agonist response remains largely independent of the absolute dose of agonist, as long as the ratio of antagonist to agonist is held constant. This general approach for limiting agonist duration under conditions in which absolute agonist dose is variable should have more general applicability.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.2
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• pp.201-208
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• 1997

It is becoming increasingly clear that the inflammatory reaction can be ascribed to a complex array of mediators generated and released from activated phagocytes. In this study, the effect of PAF on interleukin-1(IL-1) activity by rat alveolar macrophages(AM) was examined using thymocyte proliferation assay in the supernate of sample obtained after 24 hr culture. When AM were cultured with PAF alone, no change in IL-1 activity was observed. However, the combined addition of PAF and muramyl dipeptide(MDP) or lipopolysaccharide(LPS) to AM cultures markedly enhanced IL-1 activity by 2-3 fold compared with AM cultures with the stimulant alone in a concentration dependent fashion. The peack effect was found at $10^{-8}$ M PAF with MDP and $10^{-14}$ M PAF with LPS. the effect of PAF was also tested in silica, toxic respirable dust, -added AM cultures as well as in the cultures containing bacterial compounds. Although silica did not stimulate the IL-1 activity, PAF could enhance IL-1 activity by 2 fold above the value of the silica-treated AM cultures with the peak response at $10^{-12}$ M PAF. Optimal enhancement of IL-1 activity occured when MDP and PAF were present together at the initiation of the 24 hr AM cultures. Additionaly, the biologically inactive precursor/metabolite of PAF, lyso-PAF failed to induce enhancement of IL-1 activity. When the specific, but structurally different PAF receptor antagonists, BN 52021($10^{-5}$ M) and CV 3988($10^{-5}$ M) was treated 15 min before addition of PAF($10^{-8}$ M) and MDP$(10\;{\mu}g/ml)$ to the AM cultures, it markedly inhibited the enhancement of IL-1 activity induced by PAF. The effects of these PAF antagonists were also observed in LPS$(10\;{\mu}g/ml)$-stimulated cells. Collectively, these data suggest that PAF enhances IL-1 activity by interaction with a specific receptor.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.11
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• pp.1541-1545
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• 2006

The polymorphism of insulin-like growth factor I receptor (IGFIR) gene in 12 pig breeds (total n = 593) was detected by PCR-SacII-restriction fragment length polymorphism and allele A (379 bp) or allele B (235 bp and 144 bp) observed. In the studied breeds, it was found that European pigs principally carried allele A, while Chinese native pig breeds principally carried allele B. In addition, the role of pig IGFIR was investigated in 156 Wanbai pigs and 212 Large Yorkshire pigs. Growth related variables including body weight at birth, 2-, 4- and 6-mo of age and backfat thickness and lean percentage estimated by ultrasonography at 6-mo of age were recorded in analyzing the association between IGFIR gene polymorphism and growth traits. AA-genotype pigs exhibited greater (p<0.05) body weights (BW) at birth, 2- and 6-mo of age, but not at 4-mo of age, than those of the BB-genotype in Wanbai and Yorkshire breeds. Moreover, in the Yorkshire breed, AA-genotype pigs had less backfat thickness (p<0.05) and greater lean percentage (p<0.01) than the BB genotype. Based on these results, it is necessary to do more studies on IGFIR before introducing the IGFIR locus into breeding programs.

• Journal of Life Science
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• v.28 no.2
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• pp.265-273
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• 2018

Estrogen (E2) is involved in the development and progression of breast cancer and is mediated by estrogen receptor (ER). ER plays important roles in cellular proliferation, migration, invasion and causing drug resistance through diverse cross-talks with epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathways in breast cancer cells. Breast cancer is caused mainly by break-down of homeostasis of endocrine signaling pathways especially by the uncontrolled expression and increased activities of E2/IGF-1/EGF, ER/G-protein estrogen receptor (GPER)/IGF-1R/EGFR and their intracellular signaling mediators. These changes influence the complex cross-talk between E2 and growth factors' signaling, eventually resulting in the progression of cancer and resistance against endocrine regulators. Thus, elucidation of the molecular mechanisms in stepwise of the cross-talk between E2 and growth factors will contribute to the customized treatment according to the diverse types of breast cancer. In particular, as strategies for the treatment of breast cancer with diverse genotypes and phenotypes, there can be use of aromatase inhibitors and blockers of E2 action for the ER+ hormone-dependent breast cancer cells and use of IGF-1R/EGFR activity blockers for suppression of cancer cell proliferation from the cross-talk between E2 and growth factors. Furthermore, changes in the expression of the ECM molecules regulated by the cross-talk between ER and EGFR/IGF-1R can be used for the targeted therapeutics against the migration of breast cancer cells. Therefore, it is required for the cross-talk among the signaling pathways of ER, GPER, IGF-1R and EGFR concerning cancer progression to be elucidated in more detail at the molecular level.

• Biomolecules & Therapeutics
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• v.29 no.1
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• pp.22-30
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• 2021

Till the 21st century, fatty acids were considered as merely building blocks for triglycerides, phospholipids, or cholesteryl esters. However, the discovery of G protein-coupled receptors (GPCRs) for free fatty acids at the beginning of the 21st century challenged that idea and paved way for a new field of research, merged into the field of receptor pharmacology for intercellular lipid mediators. Among the GPCRs for free fatty acids, free fatty acid receptor 4 (FFA4, also known as GPR120) recognizes long-chain polyunsaturated fatty acids such as DHA and EPA. It is significant in drug discovery because it regulates obesity-induced metaflammation and GLP-1 secretion. Our study reviews information on newly developed FFA4 agonists and their application in pathophysiologic studies and drug discovery. It also offers a potency comparison of the FFA4 agonists in an AP-TGF-α shedding assay.

• Journal of Oriental Neuropsychiatry
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• v.15 no.1
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• pp.77-86
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• 2004

Objective : This study was performed to investigate the agonistic activity of Chunmajeongal-tang extract to the $GABA_A/benzodiazepine$ receptor complex. Methods : Male mice and Sprague-Dawley rats were used for this experiment. Chunmajeongal-tang Prescription was extracted with 80% methanol, evaporated in vacuo and dried with freeze dryer. The agonistic activity to the GABA/ benzodiazepine receptor complex and GABA transaminase activity were measured in vitro. Results : Chunmajeongal-tang extract inhibited dose-dependently the binding of [3H]Ro15-1788, an antagonist on GABA/benzodiazepine receptor complex, in rat cerebral cortices, showing $82.4{\pm}4.12%$ inhibition at a dose of 5.0 mg/kg. This extract inhibited dose-dependently the binding of [3H]flunitrazepam, an agonist on GABA/benzodiazepine receptor complex, in rat cerebral cortices, showing $5.6{\pm}1.24%$ inhibition. Furthermore, Chunmajeongal-tang extract inhibited the binding of [3H]flunitrazepam in the presence of GABA/NaCI with $13.2{\pm}0.44%$ inhibition, its inhibitory effect exhibited a positive GABA shift, which means that this extract activates a GABAergic neurotransmission.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.2
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• pp.77-86
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• 2022

The effect of PHAR-DBH-Me, a cannabinoid receptor agonist, on different cardiovascular responses in adult male rats was analyzed. The blood pressure was measured directly and indirectly. The coronary flow was measured by Langendorff preparation, and vasomotor responses induced by PHAR-DBH-Me in aortic rings precontracted with phenylephrine (PHEN) were analyzed. The intravenous injection of the compound PHAR-DBH-Me (0.018-185 ㎍/kg) resulted in decreased blood pressure; maximum effect was observed at the dose of 1,850 ㎍/kg. A concentrationdependent increase in the coronary flow was observed in a Langendorff preparation. In the aortic rings, with and without endothelium, pre-contracted with PHEN (10^-6 M), the addition of PHAR-DBH-Me to the superfusion solution (10^-12-10^-5 M), produced a vasodilator response, which depends on the concentration and presence of the endothelium. L-NAME inhibited these effects. Addition of CB₁ receptor antagonist (AM 251) did not modify the response, while CB₂ receptor antagonist (AM630) decreased the potency of relaxation elicited by PHAR-DBH-Me. Indomethacin shifted the curve concentration-response to the left and produced an increase in the magnitude of the maximum endothelium dependent response to this compound. The maximum effect of PHAR-DBH-Me was observed with the concentration of 10^-5 M. These results show that PHAR-DBH-Me has a concentration-dependent and endothelium-dependent vasodilator effect through CB₂ receptor. This vasodilation is probably mediated by the synthesis/release of NO. On the other hand, it is suggested that PHAR-DBH-Me also induces the release of a vasoconstrictor prostanoid.