성주기에 따른 자궁근 수축력의 변화에 관한 연구 : 성홀몬 및 약물들의 영향

김인교,박혜수,구본숙,이익호,Kim, In-Kyo,Park, Hye-Soo,Koo, Bon-Sook,Lee, Ek-Ho 대한생리학회 1987 대한생리학회지 Vol.21 No.1

It has been well known that estrogens stimulate the uterine contractility and progestins inhibit it. Then, one may expect that the uterine contractility and sensitivities to oxytocin (OT) and prostaglandin $F_{2{\alpha}}\;(PGF_{2{\alpha}})$ would be different among the estrus cycle. These hypotheses were tested using the mature female rat. Spontaneous isometric contractions of isolated uterine strips $(1{\times}0.3\;cm)$ from cyclic rats in various stages of the estrus cycle, bilateral ovarectomized rats and hypophysectomized rats were recorded in absence or presence with $estradiol-17{\beta}\;(E_2)$, progesterone $(P_4)$, OT and $PGF_{2{\alpha}}$. The results were summarized as follows: 1) The spontaneous uterine contractile force was the highest in the estrus rat and the lowest in the ovarectomized or the hypophysectomized rat. In the proestrus rat, the contractile frequency was the lowest (2.7 beats/10 min) and the contractile duration was the longest (70 sec). In the other groups, there were no any differencies in frequency (9 beats/10 min) and in duration (30 sec). 2) OT and $PGF_{2{\alpha}}$ stimulated the uterine contractility in all groups tested except in the hypophysectomized rat in which OT failed to stimulate the uterine contraction. $PGF_{2{\alpha}}$ was more effective in stimulating the uterine contraction than OT in all groups tested except in the estrus rat. OT-induced contraction was the highest in the estrus rat and $PGF_{2{\alpha}}-induced$ contraction was the lowest in the hypophysectomized rat. 3) Uterine contractilities were not changed by the in vitro treatments of $E_2$ or $P_4$ under the influence of endogenous steroids, however, $E_2$ and $P_4$ stimulated the uterine contraction in the ovarectomized rat in which endogenous steroids were almost abolished. 4) Increased uterine contraction by the treatment of OT was suppressed by in vitro $E_2$ or $P_4$ in the estrus rat, while it was potentiated by the $P_4$ in the proestrus rat. In other groups, exogenous $E_2$ or $P_4$ did not affect the OT-induced uterine contraction. 5) $PGF_{2{\alpha}}-induced$ uterine contraction was suppressed in the ovarectomized rat by $E_2$ and $P_4$, in the diestrus and proestrus rats by $P_4$ and in the hypophysectomized rat by $E_2$. In other groups, exogenous $E_2$ or $P_4$ was ineffective in altering the $PGF_{2{\alpha}}-induced$ uterine contraction. According to the above results, it may conclude that the mechanisms of the different uterine contractility and the different uterine sensitivity to OT or $PGF_{2{\alpha}}$ according to the estrus cycle are not explicable with only the serum concentrations of steroids, OT and $PGF_{2{\alpha}}$ but also other unknown factors.

장거리 (마라톤)선수에서의 전 경기중 심박동수의 변화

김인교,이중우,하종식,유연희,최정옥,김기호,Kim, In-Kyo,Lee, Jung-Woo,Hah, Jong-Sik,Ryu, Yun-Hee,Choi, Jung-Ok,Kim, Ki-Ho 대한생리학회 1979 대한생리학회지 Vol.13 No.1

To evaluate the present status of physical fittness of Korean long distance runners, body fat, pulmonary functions, maximal oxygen intake and oxygen debt were measured in 5 elite marathoners (A group), 6 college student runners (B group) and 3 middle school student runners (C group). After laboratory tests, full course marathon running was performed in 2 elite marathoners during which their heart rates were monitored continuously. The results are summerized as follows: 1) Total body fat in all three groups are in the range of 13-15% of their body weight. 2) In all three groups, average values of various pulmonary functions were within the normal limits, but those of tidal volume were higher and respiratory rate were lower in comparison to normal values. These phenomena may represent respiratory adaptations against training. The average resting oxygen consumptions in A,B and C were $322{\pm}23$, $278{\pm}14$ and $287{\pm}16$m1/min, respectively. 3) In all three groups, resting blood pressures were in the normal range, but the resting heart rate was slightly lower in groups A $(56{\pm}3\;beats/min)$ and B $(64{\pm}2\;beats/min)$ and higher in group C $(82{\pm}9\;beats/min)$ in comparison to normal values. These changes in cardiovascular functions in marathoners may also represent adaptive phenomena. 4) During treadmill running the minute ventilation and oxygen consumption of the runners increased lineally with work load in all three groups. When the oxygen consumption was related to heart rate, it appeared to be a exponential function of the heart rate in all three groups. 5) The average maximal heart rates during maximal work were $196{\pm}3$, $191{\pm}3$ and $196{\pm}5\;beats/min$ for groups A,B and C, respectively. Maximal oxygen intakes were $84.2{\pm}3.3\;ml/min/kg$ in group A, $65.2{\pm}1.1\;ml/min/kg$ in group B and $58.7{\pm}0.4\;ml/min/kg$ in group C. 6) In all three groups, oxygen debts and the rates of recovery of heart rate after treadmill running were lower than those of long ditsance runners reported previously. 7) The 40 km running time in 2 elite marathoners was recorded to be $2^{\circ}42'25'$, and their mean speed was 243 m/min (ranged 218 to 274 m/min). The heart rate appeared to increase lineally with running speed, and the total energy expenditure during 40 km running was approximately 1360.2 Calories. From these it can be speculated that if their heart rates were maintained at 166 beats/min during the full course of marathon running, their records would be arround $2^{\circ}15'$. Based on these results, we may suspect that a successful long distance running is, in part, dependent on the economical utilization of one's aerobic capacity.

적출된 토끼와 자라심장에서의 $Ca^{++}$ Pool

김인교,이중우,강두희,Kim, In-Kyo,Lee, Joong-Woo,Kang, Doo-Hee 대한생리학회 1975 대한생리학회지 Vol.9 No.1

From the study of movements of $Ca^{++}$ in frog cardiac muscle, Niedergerke (1963) postulated that $Ca^{++}$ necessary for the cardiac contraction is stored in a specific pool. Langer et al (1967) and DeCaro (1967) also found a close relationship between the change of $Ca^{++}$ flux kinetics and the change of contractile force. According to the studies of several investigators, Ca II (Bailey and Dressel 1968) or phase I and II (Langer 1965, Langer et al 1967, 1971) in the $Ca^{++}$ washout curve was associated with cardiac contractility. This investigation was aimed to elucidate the anatomical region of the contractile active $Ca^{++}$ pool. At the same time, it was assumed in this study that $Ca^{++}$ in the sarcoplasmic reticulumn represents one of the major intracellular $Ca^{++}$ pool and cardiac contractility was also dependent on the intracellular $Ca^{++}$ concentration. Consequently, this experiment was performed at different temperatures to activate to activate inhibit the deactivating process of activated $Ca^{++}$ in the intracellular space to see if changes in the contractility decay curve existed at different temperatures. The isolated hearts of rabbits and turtles (Amyda maackii) were attached to the perfusion apparatus according to the method employed by Bailey and Dressel (1968). The isolated hearts were initally perfused with a full Ringer solution containing 2 mg/ml of inulin for 1 hr, and then $Ca^{++}$ and inulin-free Ringer solution was perfused while the isometric tension was recorded and a serial sample of perfusion fluid dripping from the cardiac apex was collected for 10 sec throughout experimental period. The above procedure was performed at $23^{\circ}C$, $30^{\circ}C$ and $38^{\circ}C$ on the rabbit heart and $10{\sim}13^{\circ}C$, $10^{\circ}C$, $25^{\circ}C$, $30^{\circ}C$ and $35^{\circ}C$ on the turtle heart. After determination of $Ca^{++}$ and inulin concentration of the samples, the $Ca^{++}$, inulin washout curve and the contractile tensin decay curve were analysed according to the method of Riggs (1963). The results were summarized as follows; 1. In the rabbit heart, there are 2 inulin compartments, 3 $Ca^{++}$ compartments and sing1e exponential decay of contractile tension. In the turtle heart, there are $1{\sim}2$ inulin compartments, $1{\sim}2$ $Ca^{++}$ compartments and $1{\sim}2$ phases of contractile tension decay. The fact that the inulin space was divided into 3 compartments in the washout curve in these hearts indicates the presence of heterogeneity in cardiac perfusion, i.e., overfused and underperfused area. 2. Ca I a9d Ca II in these hearts were found to have $Ca^{++}$ in the ECF compartments because their half times in the washout curves were far smaller than those of the inulin washout curves in the rabbit heart and similar to those of the inulin washout curves in the turtle heart. Ca III in the rabbit heart may have originated from the intracellular $Ca^{++}$ store. But no Ca III in the turtle heart was found. This may be due to the fact that the iutracellular $Ca^{++}$ pool in the turtle heart was too small to detect using this experimental procedure since sarcoplasmic reticulumn in the turtle heart is poorly developed. 3. In the rabbit heart, there were no chages in the half time of Ca I, Ca II, inulin I and inulin II at different temperatures, but the half time of Ca III was significantly prolonged at lower temperatures, and the half time of the contractile tension decay tended to be prolonged at lower temperatures but this was not significant. In the turtle heart, there were no changes in the half time of Ca I, Ca II, inulin 1, inulin II and phase I of the contractile

황체퇴화시 황체막 $Na^+-K^+$-ATPase 활성도의 변화

김인교,연동수,이승일,Kim, In-Kyo,Yeoun, Dong-Soo,Lee, Syng-Ill 대한생리학회 1982 대한생리학회지 Vol.16 No.2

Slices of rat corpora lutea(CL) incubated with. prostaglandin $F_{{2{\alpha}}}(PGF_{2{\alpha}})$ in Krebs-Hensenleit (K-H) Ringer solution showed a decrease in $Na^+-K^+$-ATPase activity after 60 min of incubation. However, $PGF_{2{\alpha}}$ in vitro did not alter $Na^+-K^+$-ATPase activity of isolated luteal membrane fractions. Following $PGF_{2{\alpha}}$ induced in vivo luteal regression, reduction of Vmax an elevation of the activation energy above transition temperature of the lipid phase of the membrane occurred without changes of Km, optimum pH and transition temperature. These results suggest that reduction of $Na^+-K^+$-ATPase activity after $PGF_{2{\alpha}}$ treatment may be due to the reduction of the number of enzyme molecules or to masking of the active site of the enzyme without any change in enzyme characteristics. In addition, a change in membrane bound enzyme activity may be an early step in $PGF_{2{\alpha}}$ induced luleolysis.

적출된 토끼와 자라심장에서의 Ca⁺⁺ Pool

김인교(Kim, In-Kyo),이중우(Lee, Joong-Woo),강두희(Kang, Doo-Hee) 대한생리학회 1975 대한생리학회지 Vol.9 No.1

From the study of movements of Ca⁺⁺ in frog cardiac muscle, Niedergerke (1963) postulated that Ca⁺⁺ necessary for the cardiac contraction is stored in a specific pool. Langer et al (1967) and DeCaro (1967) also found a close relationship between the change of Ca⁺⁺ flux kinetics and the change of contractile force. According to the studies of several investigators, Ca II (Bailey and Dressel 1968) or phase I and II (Langer 1965, Langer et al 1967, 1971) in the Ca⁺⁺ washout curve was associated with cardiac contractility. This investigation was aimed to elucidate the anatomical region of the contractile active Ca⁺⁺ pool. At the same time, it was assumed in this study that Ca⁺⁺ in the sarcoplasmic reticulumn represents one of the major intracellular Ca⁺⁺ pool and cardiac contractility was also dependent on the intracellular Ca⁺⁺ concentration. Consequently, this experiment was performed at different temperatures to activate to activate inhibit the deactivating process of activated Ca⁺⁺ in the intracellular space to see if changes in the contractility decay curve existed at different temperatures. The isolated hearts of rabbits and turtles (Amyda maackii) were attached to the perfusion apparatus according to the method employed by Bailey and Dressel (1968). The isolated hearts were initally perfused with a full Ringer solution containing 2 mg/ml of inulin for 1 hr, and then Ca⁺⁺ and inulin-free Ringer solution was perfused while the isometric tension was recorded and a serial sample of perfusion fluid dripping from the cardiac apex was collected for 10 sec throughout experimental period. The above procedure was performed at 23℃, 30℃ and 38℃ on the rabbit heart and 10 ~ 13℃, 10℃, 25℃, 30℃ and 35℃ on the turtle heart. After determination of Ca⁺⁺ and inulin concentration of the samples, the Ca⁺⁺, inulin washout curve and the contractile tensin decay curve were analysed according to the method of Riggs (1963). The results were summarized as follows; 1. In the rabbit heart, there are 2 inulin compartments, 3 Ca⁺⁺ compartments and sing1e exponential decay of contractile tension. In the turtle heart, there are 1 ~ 2 inulin compartments, 1 ~ 2 Ca⁺⁺ compartments and 1 ~ 2 phases of contractile tension decay. The fact that the inulin space was divided into 3 compartments in the washout curve in these hearts indicates the presence of heterogeneity in cardiac perfusion, i.e., overfused and underperfused area. 2. Ca I a9d Ca II in these hearts were found to have Ca⁺⁺ in the ECF compartments because their half times in the washout curves were far smaller than those of the inulin washout curves in the rabbit heart and similar to those of the inulin washout curves in the turtle heart. Ca III in the rabbit heart may have originated from the intracellular Ca⁺⁺ store. But no Ca III in the turtle heart was found. This may be due to the fact that the iutracellular Ca⁺⁺ pool in the turtle heart was too small to detect using this experimental procedure since sarcoplasmic reticulumn in the turtle heart is poorly developed.

황체퇴화시 황체막 Na⁺-K⁺-ATPase 활성도의 변화

김인교(Kim, In-Kyo),연동수(Yeoun, Dong-Soo),이승일(Lee, Syng-Ill) 대한생리학회 1982 대한생리학회지 Vol.16 No.2

Slices of rat corpora lutea(CL) incubated with. prostaglandin F_2α(PGF_2α) in Krebs-Hensenleit (K-H) Ringer solution showed a decrease in Na⁺-K⁺-ATPase activity after 60 min of incubation. However, PGF_2α in vitro did not alter Na⁺-K⁺-ATPase activity of isolated luteal membrane fractions. Following PGF_2α induced in vivo luteal regression, reduction of Vmax an elevation of the activation energy above transition temperature of the lipid phase of the membrane occurred without changes of Km, optimum pH and transition temperature. These results suggest that reduction of Na⁺-K⁺-ATPase activity after PGF_2α treatment may be due to the reduction of the number of enzyme molecules or to masking of the active site of the enzyme without any change in enzyme characteristics. In addition, a change in membrane bound enzyme activity may be an early step in PGF_2α induced luleolysis.

Gonadotropins, Prostaglandin $F_{2{\alpha}}$ 및 Ouabain이 황체막의 $Ca^{++}-ATPase$ 활성도에 미치는 영향

구본숙,김인교,Koo, Bon-Sook,Kim, In-Kyo 대한생리학회 1987 대한생리학회지 Vol.21 No.1

It has been reported that the luteal function may be regulated by the intracellular $Ca^{++}$ level which may be adjusted partially by the high affinity $Ca^{++}-ATPase$ in luteal cell membranes. Then, one may expect that luteotropic and/or luteolytic agents, such as gonadotropins, prostaglandin $F_{2{\alpha}}\;(PGF_{2{\alpha}})$ and ouabain, affect the intracellular $Ca^{++}$ level. In this present study, therefore, we examined the effects of luteinizing hormone (LH, or human chorionic gonadotropin, hCG), $PGF_{2{\alpha}}$ and ouabain on the kinetic properties of the high affinity $Ca^{++}-ATPase$ in light membrane, heavy membrane, and microsomal fractions from the highly luteinized ovary. LH (or hCG) increased the affinity and the Vmax for $Ca^{++}$ both in light membrane and heavy membrane. $PGF_{2{\alpha}}$ increased the Vmax in light membrane and decreased the Km in heavy membrane for $Ca^{++}$ at low concentration $(5\;{\mu}g/ml)$. At higher concentration, however, $PGF_{2{\alpha}}$ oppositly affected on kinetic properties, that shown at low concentration. Ouabain, a potent inhibitor of $Na^+-K^+-ATPase$, increased the Km at high concentration $(10^{-4}\;M)$, however, decreased the Vmax for $Ca^{++}$ in light membrane at low concentration $(10^{-6}\;M)$. Also, ouabain increased the Km for $Ca^{++}$ in heavy membrane without changes in the Vmax at both concentrations. It seems that LH and low dose of $PGF_{2{\alpha}}$ increase the intracellular $Ca^{++}$ level and cause in activation of $Ca^{++}-ATPase$, however, higher dose of $PGF_{2{\alpha}}$ and ouabain inhibit directly $Ca^{++}-ATPase$ activity and result in increase in intracellular $Ca^{++}$ level. According to the above results, we suggest that luteotropic and/or luteolytic agents regulate the luteal progesterone $(P_4)$ production through two different pathways; one is cyclic adenosine monophosphate (cAMP)-dependent and another is $Ca^{++}-dependent$. Intracellula. $Ca^{++}$ level regulated by the high affinity $Ca^{++}-ATPase$ may affect both pathways in a time-dependent fashion. LH (or hCG) acts on the luteal $P_4$ production via both pathways. The initial step is $Ca^{++}$ dependent, and the late step is cAMP dependent. $PGF_{2{\alpha}}$ and ouabain increase the intracellular $Ca^{++}$ concentration so that basal luteal $P_4$ production is increased and LH-stimulated $P_4$ production is inhibited by the inhibiting LH-dependent adenylate cyclase activity.

$Na^+$농도 및 삼투압의 변화가 신피질 절편에서의 Renin분비에 미치는 영향

강선옥,김인교,강두희,Kang, Sun-Ok,Kim, In-Kyo,Kang, Doo-Hee 대한생리학회 1976 대한생리학회지 Vol.10 No.1

Most investigators have come to stress two different concepts of mechanism controlling renin release; intrarenal baroreceptor theory and the macula densa theory(Vander 1967, Thurau and Masson 1974). In the macula densa theory, the specific macula densa parameter, most commonly suggested as a possible signal, is either the osmolality or the concentration of sodium in the tubular fluid (Thurau 1964, Vander and Miller 1964, Reeves and Sommers 1965). It has been shown that sodium plays an important role in the release of renin either in vivo (Thurau 1964, Vander and Miller 1964, Thurau et al 1972) or in vitro experiments(Oelkers et al 1970, Hammerson et al 1971, Michelakis 1971). On the other hand the osmolality appears to have no effect on the release of renin in vivo (Vander 1967, Thurau and Masson 1974). However, there has been little attempt to study the effect of osmolality on in vitro renin release. We therefore undertook the present investigation to elucidate the effect of osmolality on renin release and to further test the sodium influence upon the release of renin from isolated kidney slice preparations. Isolated renal cortical slices were washed with normal Krebs-Hensenleit bicarbonate buffer solution and incubated for 30 minutes in a medium containing an appropriate concentration of sodium and osmolality. The renin released into the medium was measured by the method of radioimmunoassay(Haber et al 1969). The results obtained are as follows; 1. The release of renin from renal cortical slices was progressively inhibited as the sodium concentration in the medium increased. 2. No significant alteration in renin release was observed when osmolality of the medium was changed. These results suggest that the release of renin from the renal cortical slices is directly affected by the changes in sodium concentration in the medium, but is not influenced by the alterations in osmolality.

황체막에서의 $Ca^{++}-ATPase$의 특성

최규복,구본숙,김인교,Choi, Gyu-Bog,Koo, Bon-Sook,Kim, In-Kyo 대한생리학회 1986 대한생리학회지 Vol.20 No.2

It has been reported that the luteal function may be regulated by the intracellular calcium in luteal cells (Higuchi et al, 1976; Dorflinger et at, 1984; Gore and Behrman, 1984) which is adjusted partially by $Ca^{++}-ATPase$ activities in luteal cell membranes (Verma and Pennistion, 1981). However, the physicochemical and kinetic properties of $Ca^{++}-ATPase$ in luteal membranes were not fully characterized. This study was, therefore, undertaken to partially characterize the physicochemical and kinetic properties of $Ca^{++}-ATPase$ system in luteal membranes and microsomal fractions, known as an one of the major $Ca^{++}$ storge sites (Moore and Pastan, 1978), from the highly luteinized ovary Highly luteinized ovaries were obtained from PMSG-hCG injected immautre female rats. Light membrane and heavy membrane fractions and microsomal fractions were prepared by the differential and discontinuous sucrose density gradient centrifugation method desribed by Bramley and Ryan (1980). Light membrane and heavy membrane fractions and microsomal fractions from highly luteinized ovaries are composed of the two different kinds of $Ca^{++}-ATPase$ system. One is the high affinity $Ca^{++}-ATPase$ which is activated in low $Ca^{++}$ concentration (Km, 10-30 nM), the other is low affinity $Ca^{++}-ATPase$ activated in higher $Ca^{++}$ concentration $(K_{1/2},\;40\;{\mu}M)$. At certain $Ca^{++}$ concentrations, activities of high and low affinity $Ca^{++}-ATPase$ are the highest in light membrane fractions and are the lowest in microsomal fractions. It appeares that high affinity $Ca^{++}-ATPase$ system have 2 binding sites for ATP (Hill's coefficient; around 2 in all membrane fractions measured) and the positive cooperativity of ATP bindings obviously existed in each membrane fractions. The optimum pH for high affinity $Ca^{++}-ATPase$ activation is around S in all membrane fractions measured. The lipid phase transition temperature measured by Arrhenius plots of high affinity $Ca^{++}-ATPase$ activity is around $25^{\circ}C$. The activation energies of high affinity $Ca^{++}-ATPase$ below the transition temperature are similar in each membrane fractions, but at the above transition temperature, it is the hightest in heavy membrane fractions and the lowest in microsomal fractions. According to the above results, it is suggested that intracellular $Ca^{++}$ level, which may regulate the luteal function, may be adjusted primarily by the high affinity $Ca^{++}-ATPase$ system activated in intracellular $Ca^{++}$ concentration range $(below\;0.1\;{\mu}M)$.

Gonadotropins, Prostaglandin F_2α 및 Ouabain이 황체막의 Ca⁺⁺}-ATPase 활성도에 미치는 영향

구본숙(Koo, Bon-Sook),김인교(Kim, In-Kyo) 대한생리학회 1987 대한생리학회지 Vol.21 No.1

It has been reported that the luteal function may be regulated by the intracellular Ca⁺⁺ level which may be adjusted partially by the high affinity Ca⁺⁺-ATPase in luteal cell membranes. Then, one may expect that luteotropic and/or luteolytic agents, such as gonadotropins, prostaglandin F_2α (PGF_2α) and ouabain, affect the intracellular Ca⁺⁺ level. In this present study, therefore, we examined the effects of luteinizing hormone (LH, or human chorionic gonadotropin, hCG), PGF^2α and ouabain on the kinetic properties of the high affinity Ca⁺⁺-ATPase in light membrane, heavy membrane, and microsomal fractions from the highly luteinized ovary. LH (or hCG) increased the affinity and the Vmax for Ca⁺⁺ both in light membrane and heavy membrane. PGF^2α increased the Vmax in light membrane and decreased the Km in heavy membrane for Ca⁺⁺ at low concentration (5 μg/ml). At higher concentration, however, PGF^2α oppositly affected on kinetic properties, that shown at low concentration. Ouabain, a potent inhibitor of Na⁺-K⁺-ATPase, increased the Km at high concentration (10^-4 M), however, decreased the Vmax for Ca⁺⁺ in light membrane at low concentration (10^-6 M). Also, ouabain increased the Km for Ca⁺⁺ in heavy membrane without changes in the Vmax at both concentrations. It seems that LH and low dose of PGF^2α increase the intracellular Ca⁺⁺ level and cause in activation of Ca⁺⁺-ATPase, however, higher dose of PGF^2α and ouabain inhibit directly Ca⁺⁺-ATPase activity and result in increase in intracellular Ca⁺⁺ level. According to the above results, we suggest that luteotropic and/or luteolytic agents regulate the luteal progesterone (P₄) production through two different pathways; one is cyclic adenosine monophosphate (cAMP)-dependent and another is Ca⁺⁺-dependent. Intracellula. Ca⁺⁺ level regulated by the high affinity Ca⁺⁺-ATPase may affect both pathways in a time-dependent fashion. LH (or hCG) acts on the luteal P₄ production via both pathways. The initial step is Ca⁺⁺ dependent, and the late step is cAMP dependent. PGF^2α and ouabain increase the intracellular Ca⁺⁺ concentration so that basal luteal P₄ production is increased and LH-stimulated P₄ production is inhibited by the inhibiting LH-dependent adenylate cyclase activity.