• YAKHAK HOEJI
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• v.38 no.1
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• pp.67-77
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• 1994

In order to investigate the feasibility of transmucosal delivery of the model peptide, LHRH, metabolism of LHRH and inhibition effect of medium chain fatty acid salts were studied in rabbit mucosal homogenate. LHRH incubated in homogenates of rectal(RE), nasal(NA) and vaginal(VA) mucosa were assayed by HPLC. Five to six degradation products of LHRH were deterted and the degradation of LHRH$(500\;{\mu}g/ml)$ followed the first order kinetics. The main degradation products were found as $LHRH^{1-5}(M-I)$, $LHRH^{1-3}(M-II)$ and $LHRH^{1-6}(M-III)$ by the method of amino acid analysis. The half-lives of LHRH in the mucosal homogenates were found to be less than 20 min at protein concentration of 2.5 mg/ml with the order of VA>NA>RE mucosal homogenate. Medium chain fatty acid salts such as sodium caprylate $(C_8)$, sodium caprate $(C_{10})$ and sodium laurate $(C_{12})$ at the concentration of $0.5%{\sim}1.0%$ inhibit the proteolysis of LHRH significantly. The addition of sodium laurate(0.5%) into the NA and VA mucosal homogenates protected LHRH completely from the degradation.

• YAKHAK HOEJI
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• v.38 no.2
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• pp.202-210
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• 1994

To investigate the feasibility of mucosal delivery of $[D-Ala^6]$ LHRH, a potent analogue of LHRH, enzymatic proteolysis of $[D-Ala^6]$ LHRH and inhibitory effect of medium chain fatty acid salts(MFA) were studied using rabbit mucosal homogenate. $[D-Ala^6]$ LHRH incubated in homogenates of rectal(RE), nasal(NA) and vaginal(VA) mucosa were assayed by HPLC. The degradation of $[D-Ala^6]$ LHRH followed the first order kinetics. The degradation products were found as $[D-Ala^6]$ $LHRH^{1-7}$(m-i), to a lesser extent, $[D-Ala^6]$ $LHRH^{1-9}$(m-ii) and $[D-Ala^6]$ $LHRH^{1-3}$(m-iii) by the method of amino acid analysis(PITC method). The formation of$[D-Ala^6]$ $LHRH^{1-7}$ was not inhibited by the addition of disodium ethylenediaminetetraacetic acid but inhibited by sodium tauro-24,25-dihydrofusidate, suggesting that endopeptidase 24.11(EP 24.11) cleaves the $Leu^7-Arg^8$ bond of $[D-Ala^6]$ LHRH and is the primary $[D-Ala^6]$ LHRH degrading enzyme. The patterns of $[D-Ala^6]$ LHRH degradation indicated that EP 24.11 exists in each mucosal homogenate with the order of RE>NA>VA. MFA significantly inhibited the proteolysis of $[D-Ala^6]$ LHRH. The addition of sodium caprate(1.0%) or sodium laurate(0.5%) to the each mucosal homogenate completely protected $[D-Ala^6]$ LHRH from the degradation.

• The Korean Journal of Physiology
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• v.10 no.1
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• pp.35-40
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• 1976

In an attempt to examine the effect of ginseng on sodium transport across the biological membrane, we have studied effects of ginseng alcohol extract on the short-circuit current(SCC) and the $Na^+-K^+$-activated ATPase activity in isolated frog skin preparations. 1. Ginseng alcohol extract applied to the mucosal surface of the frog skin significantly increased SCC at low concentration($1{\sim}10mg%$) but decreased SCC at higher concentration($50{\sim}250mg%$). 2. Similarly, when the drug was added to the serosal bathing medium, the SCC was stimulated at low doses($5{\sim}25mg%$) and inhibibited at high doses($50{\sim}250mg%$). 3. $Na^+-K^+$-activated ATPase activity of the frog skin epidermal homogenate was significantly inhibited by ginseng alcohol extract, the effect being proportional to the concentration of the drug in the incubation mixture. These results may suggest that a low dose of ginseng alcohol extrat enhances the transepithelial sodium transport probably by increasing the permeability of outer membrane of the transporting cell to sodium ion, whereas a high dose of drug reduces the sodium transport primarly by inhibiting $Na^+-K^+$ ATPase mediated active transport step.