• 대한수의학회지
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• 제41권3호
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• pp.319-325
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• 2001

Several recent studies demonstrate that cAMP accumulation evokes marked changes in magnesium ($Mg^{2+}$) homeostasis. The goal of this study was to investigate the effect of melatonin, the principal hormone of the vertebral pineal gland, on $Mg^{2+}$ regulation in perfused guinea pig hearts. We hypothesized that melationin would regulate $Mg^{2+}$ efflux induced by adrenergic drugs and cAMP analogues because melatonin inhibites adneylate cyclase (AC) and phospholipase C(PLC) in the hearts. The $Mg^{2+}$ content in the perfusate was significantly higher in the presence than in the absence of melatonin. The addition of forskolin, isoproterenol or dimaprit to perfused hearts induced a marked $Mg^{2+}$ efflux. These effluxes were not inhibited by melatonin. The $Mg^{2+}$ efflux could also be induced by phenylephrine, a ${\alpha}_1$-adrenoceptor agonist. This phenylephrine-induced $Mg^{2+}$ efflux was inhibited by melatonin. In addition, the phenylephrine-induced $Mg^{2+}$ efflux was potentiated by PMA, a protein kinase C(PKC) activator. This $Mg^{2+}$ efflux was inhibited by melatonin. In conclusion, these data suggest that melatonin regulates $Mg^{2+}$ homeostasis and the inhibitory effect of melatonin on ${\alpha}_1$-adrenoceptor-stimulated $Mg^{2+}$ efflux may occur through an inhibition of PLC pathway in perfused guinea pig hearts.

• 대한수의학회지
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• 제40권3호
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• pp.479-487
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• 2000

Several recent studies demonstrate that receptor-mediated cAMP (adenosine 3',5'-monophosphate) production evokes marked change in magnesium ($Mg^{2+}$) homeostasis. The effects of dimaprit or/and phosphodiesterase (PDE) inhibitors on the $Mg^{2+}$ release from perfused guinea pig heart and collagenase-dispersed myocytes was studied to clarify an association of $H_2-histaminergic$ receptor-mediated $Mg^{2+}$ regulation with intracellular cAMP-degradation system. $Mg^{2+}$ efflux was stimulated in perfused hearts and myocytes by IBMX (3-isobutyl-1-methylxanthine), a calmodulin-sensitive PDE inhibitor, but not by RO 20-1724(4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone) or papaverine, cAMP-specific PDE inhibitors. $Mg^{2+}$ efflux was also be induced by dimaprit, a H-2-agonist. $Mg^{2+}$ effluxes induced by dimaprit were augmented by the presence of the PDE inhibitors. The augmentation of dimaprit-induced $Mg^{2+}$ effluxes by the PDE inhibitors were inhibited by ranitidine, a $H_2-antagonist$, and imipramine, a $Na^{+}-Mg^{2+}$ exchange inhibitor, in perfused hearts and myocytes and were also inhibited by amiloride in perfused hearts. These results suggest that the $H_2$-stimulated $Mg^{2+}$ effluxes from guinea pig heart can be regulated by the cytosolic nonspecific-dependent PDE systems and that it is induced by the $Na^{+}-Mg^{2+}$ exchanger stimulation.

• The Korean Journal of Physiology
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• 제29권2호
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• pp.203-216
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• 1995

The effects of ${\alpha}_1-adrenergic$ receptor stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force were investigated in ventricular muscles from guinea-pig hearts. Action potentials, intracellular $Na^+$ activity, and twitch force of ventricular papillary muscles were measured simultaneously under various experimental conditions. Stimulation of the ${\alpha}_1-adrenergic$ receptor by phenylephrine produced variable changes in action potential duration, a slight hyperpolarization of the diastolic membrane potential, a decrease in intracellular $Na^+$ activity, and a biphasic inotropic response in which a transient negative inotropic response was followed by a sustained positive inotropic response. These changes were blocked by prazosin, an antagonist of the ${\alpha}_1-adrenergic$ receptor, but not by atenolol, an antagonist of the ${\beta}-adrenergic$ receptor. This indicates that the changes in membrane potential, intracellular $Na^+$ activity, and twitch force are mediated by stimulation of the ${\alpha}_1-adrenergic$ receptor, but not by stimulation of ${\beta}-adrenergic$ receptor. The decrease in intracellular $Na^+$ activity was not observed in quiescent muscles, depending on the rate of the action pontentials in beating muscles. The intracellular $Na^+$ activity decrease was substantially inhibited by tetrodotoxin. However, the decrease in intracellular $Na^+$ activity was not affected by an inhibition of the $Na^+-K^+$ pump. Therefore, the decrease in intracellular $Na^+$ activity mediated by the ${\alpha}_1-adrenergic$ receptor appears to be due to a reduction of $Na^+$ influx during the action potential, perhaps through tetrodotoxin sensitive $Na^+$ channels. Our study also revealed that the decrease in intracellular $Na^+$ activity might be related to the transient negative inotropic response. The intracellular $Na^+$ activity decrease could lower intracellular $Ca^{2+}$ through the $Na^+-Ca^{2+}$ exchanger and thereby produce a decline in twitch force.

• Journal of Yeungnam Medical Science
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• 제4권1호
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• pp.81-87
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• 1987

피부사상균증의 접종방법을 표준화하기 위하여 N. gypsea "+"와 A. benhamiae "+"를 가토, 기니픽, rat, mouse에 정량적으로 접종하여 다음의 결과를 얻었다. 1. 포자의 농도가 높을수록 감염률이 높았고 입상양상이 심하고 일찍 나타나서 오래 지속되었다. 2. 난전, 소피, 강제발모, 단순빈도의 순으로 감염이 잘되어 피부손상의 정도에 비례함을 알 수 있었다. 3. 피부사상균에 대한 감수성은 기니픽, 가토, rat의 순으로 높았고 mouse는 전혀 감염되지 않았다. 4. N. gypsea "+"에 비해 A. benhamiae "+"는 감염률이 높고 입상양상이 더 심하고 빨리 진행되어 조기에 조절되었다.

• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.189-194
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• 2009

This study was designed to clarify the mechanism of the inhibitory effect of forskolin on contraction, cytosolic $Ca^{2+}$ level $([Ca^{2+}]_i)$, and $Ca^{2+}$ sensitivity in guinea pig ileum. Forskolin (0.1 nM ${\sim}$ 10 ${\mu}M$) inhibited high $K^+$ (25 mM and 40 mM)- or histamine (3 ${\mu}M$)-evoked contractions in a concentration-dependent manner. Histamine-evoked contractions were more sensitive to forskolin than high $K^+$-evoked contractions. Spontaneous changes in $[Ca^{2+}]_i$ and contractions were inhibited by forskolin (1 ${\mu}M$) without changing the resting $[Ca^{2+}]_i$. Forskoln (10 ${\mu}M$ ) inhibited muscle tension more strongly than $[Ca^{2+}]_i$ stimulated by high $K^+$, and thus shifted the $[Ca^{2+}]_i$-tension relationship to the lower-right. In histamine-stimulated contractions, forskolin (1 ${\mu}M$) inhibited both $[Ca^{2+}]_i$ and muscle tension without changing the $[Ca^{2+}]_i$-tension relationship. In ${\alpha}$-toxin-permeabilized tissues, forskolin (10 ${\mu}M$) inhibited the 0.3 ${\mu}M$ $Ca^{2+}$-evoked contractions in the presence of 0.1 mM GTP, but showed no effect on the $Ca^{2+}$-tension relationship. We conclude that forskolin inhibits smooth muscle contractions by the following two mechanisms: a decrease in $Ca^{2+}$ sensitivity of contractile elements in high $K^+$-stimulated muscle and a decrease in $[Ca^{2+}]_i$ in histamine-stimulated muscle.

• Asian-Australasian Journal of Animal Sciences
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• 제21권2호
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• pp.181-189
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• 2008

The aim of this study was to evaluate the effects of $Ca^{2+}$, $HCO_3{^-}$ and BSA on the in vitro capacitation-associated protein tyrosine phosphorylation, hyperactivation and acrosome reaction in guinea pig sperm. Caudal epididymal sperm were incubated in four different groups: modified TALP (Tyrode's albumin lactate pyruvate) or TALP without one of the medium constituents ($Ca^{2+}$, $HCO_3{^-}$ and BSA). After incubation for the required time (0 h, 0.5 h, 1 h, 3 h, 5 h, and 7 h), sperm were removed for further experiment. The capacitation effect was assessed by CTC (Chlortetracycline) staining. Western blotting and indirect immunofluorescence were used to analyze the level and localization of tyrosine phosphorylation. The results showed that guinea pig sperm underwent a time-dependent increase in protein tyrosine phosphorylation during the in vitro capacitation and the percentage of protein tyrosine phosphorylated sperm increased from 36% to 92% from the beginning of incubation to 7 h incubation. Also, there was a shift in the site of phosphotyrosine-specific fluorescence from the head of sperm to both the head and the flagellum. Moreover, an absence of $Ca^{2+}$ or $HCO_3{^-}$ inhibited in vitro hyperactivation and acrosome reaction and decreased the phosphorylation of the proteins throughout the period of in vitro capacitation. However, an absence of BSA could not influence these processes if substituted by polyvinyl alcohol (PVA) in the medium.

• The Korean Journal of Physiology and Pharmacology
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• 제12권2호
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• pp.59-64
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• 2008

In our previous study, we found that spermine and putrescine inhibited spontaneous and acetylcholine (ACh)-induced contractions of guinea-pig stomach via inhibition of L-type voltage- dependent calcium current ($VDCC_L$). In this study, we also studied the effect of spermidine on mechanical contractions and calcium channel current ($I_{Ba}$), and then compared its effects to those by spermine and putrescine. Spermidine inhibited spontaneous contraction of the gastric smooth muscle in a concentration-dependent manner ($IC_{50}=1.1{\pm}0.11mM$). Relationship between inhibition of contraction and calcium current by spermidine was studied using 50 mM high $K^+$-induced contraction: Spermidine (5 mM) significantly reduced high $K^+$ (50 mM)-induced contraction to 37${\pm}$4.7% of the control (p<0.05), and inhibitory effect of spermidine on $I_{Ba}$ was also observed at a wide range of test potential in current/voltage (I/V) relationship. Pre- and post-application of spermidine (5 mM) also significantly inhibited carbachol (CCh) and ACh-induced initial and phasic contractions. Finally, caffeine (10 mM)-induced contraction which is activated by $Ca^{2+}$-induced $Ca^{2+}$ release (CICR), was also inhibited by pretreatment of spermidine (5 mM). These findings suggest that spermidine inhibits spontaneous and CCh-induced contraction via inhibition of $VDCC_L$ and $Ca^{2+}$ releasing mechanism in guinea-pig stomach.

• The Korean Journal of Physiology
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• 제25권2호
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• pp.133-146
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• 1991

In order to elucidate systematically the effects of serotonin on gastric motility of guinea-pig, the contractile and electrical responses to serotonin were recorded using four kinds of muscle strips prepared from antral circular, antral longitudinal, fundic circular, and fundic longitudinal muscles. Experiments were performed using various methods including isometric contraction recording, transmural electrical field stimulation, junction potential recording, intracellular microelectrode technique, and partition stimulation method. The results were as follows: 1) The effect of serotonin on spontaneous contractions was inhibitory in the circular muscle strips of the antrum and fundus, while it was excitatory in the longitudinal muscle strips of the antrum and fundus. Serotonin changed mainly phasic contractions of both the circular and longitudinal muscle strips in the antrum, while it changed mainly tonic contractions of both the circular and longitudinal muscle strips in the fundus. 2) On the contractions induced by transmural nerve stimulation, serotonin decreased the amplitude in the circular muscle strips of the antrum, but it increased them in the other three groups of muscle strips(antral longitudinal, fundic circular, and fundic longitudinal). 3) On the contractions induced by direct muscle stimulation, serotonin decreased the amplitude in the circular muscle strips of the antrum and fundus. 4) In the fundic circular muscle strips serotonin potentiated excitatory junction potentials (EJPs), and in the antral circular muscle strips it evoked EJPs after inhibitory junction potentials(IJPS). 5) In the antral circular muscle strips serotonin did not affect the slow wave even at the disappearance of spontaneous contractions. On the contrary it increased the amplitude of the slow wave, when the spike component was potentiated and the second component was inhibited. 6) In the antral circular muscle strips the membrane potential was slightly hyperpolarized, but the membrane resistance was not changed. From the above results following conclusions could be made. 1) Serotonin inhibits spontaneous contractions of the circular muscle layer and it increases those of the longitudinal one, irrespective of the gastric region. 2) In the guinea-pig stomach there exists a serotoninergic facilitatory neuromodulation system which exerts its effect on cholinergically mediated contraction. 3) The excitation-contraction decoupling was observed in the effect of serotonin.

• The Korean Journal of Physiology and Pharmacology
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• 제4권3호
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• pp.227-234
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• 2000

Many reports suggest that neurotensin (NT) in the gastrointestinal tract may play a possible role as a neurotransmitter, a circulating hormone, or a modulator of motor activity. NT exerts various actions in the intestine; it produces contractile and relaxant responses in intestinal smooth muscle. This study was designed to investigate the effect of NT on motility of antral circular muscle strips in guinea-pig stomach. To assess the role of $Ca^{2+}$ influx in underlying mechanism, slow waves were simultaneously recorded with spontaneous contractions using conventional intracellular microelectrode technique. At the concentration of $10^{-7}$ M, where NT showed maximum response, NT enhanced the magnitude $(863{\pm}198%,\;mean\;SEM,\;n=13)$ and the frequency $(154{\pm}10.3%,\;n=11)$ of spontaneous contractions. NT evoked a slight hyperpolarization of membrane potential, tall and steep slow waves with abortive spikes $(278{\pm}50%,\;n=4).$ These effects were not affected by atropine $(2\;{\mu}M),$ guanethidine $(2\;{\mu}M)$ and tetrodotoxin (0.2μM). NT-induced contractile responses were abolished in $Ca^{2+}-free$ solution and reduced greatly to near abolition by $10\;{\mu}M$ of verapamil or 0.2 mM of $CdCl_2.$ Verapamil attenuated the effects of NT on frequency and amplitude of the slow waves. Taken together, these results indicate that NT enhances contractility in guinea-pig gastric antral circular muscle and $Ca^{2+}$ influx through the voltage-operated $Ca^{2+}$ channel appears to play an important role in the NT-induced contractile mechanism.

• The Korean Journal of Physiology
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• 제22권2호
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• pp.207-218
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• 1988

Effects of 1, 4-dihydropyridine compounds, such as nifedipine, nisoldipine, nitrendipine, and nimodipine which were calcium antagonists on the normal and Ca-dependent, slow channel mediated action potentials in the guinea pig's papillary muscle were investigated. The glass microelectrode was impaled into a papillary muscle cell for measurements of potential changes with the simultaneous tracing of isometric contraction. The concentration of Ca antagonists were 1 mg/l (nifedipine and nisoldipine), 2 mg/l (nitrendipine and nimodipine), which showed the maximal inhibition of isometric contraction (above 90%) and simultaneous effects on the normal action potentials and only the halves of those concentrations were sufficient to observe the effects on the calcium action potentials. The data for analysis were only chosen when the microelectrode was maintained in a cell throughout the experiments. 1, 4-Dihydropyridine compounds decreased the action potential duration but did not affect the resting membrane potential, overshoot, and upstroke velocity of the normal action potentials with the decrease in the isometric contraction. And with the decrease in the area and amplitude of isometric contraction, the area, amplitude, upstroke velocity and duration of Ca action potential was decreased. But the differences in the effects of the Ca antagonists were not observed. Therefore it is inferred that the changes in normal and Ca action potential induced by the 1, 4-dihydropyridine compounds with a common chemical structure would be caused by the slow inward Ca-current, not by a fast Na-current.