• The Korean Journal of Pain
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• v.21 no.3
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• pp.179-186
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• 2008

Background: The adrenergic nervous system in the spinal cord contributes to the development of neuropathic pain after nerve injury. Brain derived neurotrophic factor may facilitate the sympathetic change in the spinal cord and influence the state of neuropathic pain. We probed the effect of chronic repetitive administration of systemic 4-methylcatechol, which is known to be a neurotrophic factor inducer, in a spinal nerve ligation model. Methods: We made the rat neuropathic pain model by the ligation of the L5 spinal nerve. Intraperitoneal 4-methylcatechol ($10{\mu}g/kg$) or the same volume of saline wasadministrated twice daily just after the operation for 7 days. The tactile allodynia was measured by using von Frey filaments and its change was followed up from 3 days after SNL. The lumbosacral enlargement of the spinal cord was taken out and the mRNA contents of the ${\alpha}_2-adrenoceptor$ subtypes were measured by real time polymerase chain reaction and this was then compared with the control groups. The antiallodynic effect of intrathecal clonidine (3, 10, $30{\mu}g$) was evaluated and compared in the 4-methylcatechol treated rats and the control rats. Results: The expression of the ${\alpha}_{2A}$ and ${\alpha}_{2C}$ adrenoceptor subtypes did not change after 4-methylcatechol treatment. Intrathecal clonidine showed an earlier and better effect at the highest dose ($30{\mu}g$ intrathecal), but not with any other doses. Conclusions: Chronic intraperitoneal administration of 4-methylcatechol may improve the effect of intrathecal clonidine, but we could not prove the increase of ${\alpha}_{2A}$ and ${\alpha}_{2C}$ adrenoceptors in the spinal cord of 4-methylcatechol treated rats.

• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.59-67
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• 1982

1) Oxymetazoline, which has been known as an agonist for${\alpha}_1-adrenoceptor$ in various peripheral tissues, caused a pressor response in urethane-anesthetized rabbits when given intra-ventricularly. This pressor response was little affected by pretreatment of rabbits with i.v. guanethidine or chlorisondamine, but it was weakened in rabbits pretreated with either of i.v. phentolamine or guanethidine and chlorisondamine and in guanethidine-pretreated adrenal-ligated rabbits. 2) The pressor to intraventricular oxymetazoline was markedly attenuated by intraventricular pretreatment with prazosin, whereas intraventricular pretreatment with yohimbine or piperoxan did not affect this response. 3) Reserpine-pretreated rabbits also responded with hypertension to intraventricular oxymetazoline, which was markedly diminished by pretreatment with intraventricular prazosin but not affected by yohimbine. 4) Oxymetazoline, given intravenously, produced a pressor response in both whole and spinal rabbits. Intravenous prazosin, phentolamine and yohimbine, in this order, showed greater antagonizing effect to this pressor response. 5) The results indicate that oxymetazoline acts an agonist for ${\alpha}_1-adrenoceptors$ in the rabbit brain participating in the regulation of the blood pressure and in the vasculature of rabbits.

• The Korean Journal of Physiology
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• v.24 no.1
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• pp.67-76
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• 1990

The contractile mechanisms of serotonin were investigated in the renal artery of a rabbit. The helical strips of isolated renal artery were immersed in the normal or $Ca^{2+}$-free tris-buffered Tyrode's solution, which was equilibrated with 100% $O_{2}$ at $35^{\circ}C$. The contraction by serotonin or norepinephrine (NE) began at $1{\times}10^{-7}\;M$ and reached the maximal contraction at $1{\times}10^{-5}\;M$. The maximal contraction by serotonin corresponded to $58.1{\pm}4.2%$ of maximal contraction by NE. Cyproheptadine, a serotonin receptor blocker, shifted the concentration-response curve to the right without any reduction in the maximum response but shifted that of NE to the right with reduction in maximum response. And phentolamine, an ${\alpha}-receptor$ blocker, shifted the concentration-response curve of serotonin or NE without any reduction in maximum responses. The $pA_{2}$ values for cyproheptadine against serotonin and NE were $10.35{\pm}0.04$ and $8.45{\pm}0.13$, respectively. The $pA_{2}$ values for phentolamine against serotonin and NE were $6.87{\pm}0.04$ and $8.14{\pm}0.08$, respectively. after the pretreatment with 6-hydroxydopamine, the contraction induced by 100 mM $K^{+}$, tyramine and serotonin reduced to $83.0{\pm}2.0$, $26.8{\pm}6.2$ and $82.0{\pm}3.5%$ of control, respectively. The contraction by serotonin in the $Ca^{2+}$-free Tyrode's solution was increased and sustained with the addition of $Ca^{2+}$ extracellulary. The serotonin-sensitive intracellular $Ca^{2+}$ pool was depleted completely by the pretreatment with NE, but the NE-sensitive intracellular $Ca^{2+}$ pool was depleted partially by the pretreatment with serotonin. From the above results, it is suggested that the contraction induced by serotonin in the renal artery of a rabbit may be due to mechanisms in which serotonin acts directly on specific serotonin receptors and also acts indirectly on ${\alpha}-adrenoceptors$ by displacing NE from neuronal stores.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.170-170
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• 1998

In order to discover new types of 5-hydroxytryptamine antagonists, we have devoted our attention to investigating naturally occurring compounds having anti-5HT activity in vitro. Recently, ${\gamma}$-mangostin [1,3,6,7-tetrahydroxy-2,8-bis(3-methyl-2-bytenyl)-9H-xanthen-9-one] from the fruit hull of Garcinia mangostana Linn has been shown to be a selective antagonist for 5-hydroxytryptamine$_{2A}$ receptors in smooth muscle and platelets. It is of interesting that y-mangostin which does not have a nitrogen atom, possesses marked 5-$HT_{2A}$ receptor blocking activity. The present study was undertaken to investigate the effects of ${\gamma}$-mangostin on central 5-HT receptors by using animal behavioural models. Intracerebronventricular injection of ${\gamma}$-mangostin (10-40n mol/mouse) inhibited 5-fluoro-${\alpha}$-methyltryptamin (5-FMT) (45 mg kg$^{-1}$, i.p.)-induced head-twitch response in mice in the presence or absence of citalopram (5-HT-uptake inhibitor). Neither the 5-FMT- nor the 8-hydroxy-2-( di-n-propylamino )tetralin (5-HT$_{1A}$-agonist)-induced 5-HT syndrome (head weaving and hindlimb abduction) was affected by ${\gamma}$-mangostin. The locomotor activity stimulated by 5-FMT through the activation of at-adrenoceptors did not alter in the presence of ${\gamma}$-mangostin. 5-HT-induced inositol phosphates accumulation in mouse brain slices was abolished by ketanserin. ${\gamma}$-Mangostin caused a concentration-dependent inhibition of the inositol phosphates accumulation and the binding of [$^3H$]-spiperone, a specific 5-$HT_{2A}$ receptor antagonist, to mouse brain membranes. Kinetic analysis of the [$^H3$]-spiperone binding revealed that ${\gamma}$-mangostin increased the $_{d}$ value without affecting the $B_{max}$ value, indicating the mode of the competitive nature of the inhibition by ${\gamma}$-mangostin. These results suggest that ${\gamma}$-mangostin inhibits 5-FMT-induced head-twitch response in mice by blocking 5-$HT_{2A}$ receptors not by blocking the release of 5-HT from the central neurone. ${\gamma}$-Mangostin is a promising 5-$HT_{2A}$ receptors antagonist in the central nervous system.m.

• The Korean Journal of Pharmacology
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• v.20 no.2
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• pp.7-14
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• 1984

In pithed rats, rising in diastolic blood pressure by clonidine, when intravenously injected, is expressed as the postsynaptic action, and inhibitory action on electrical stimulation-induced tachycardia by clonidine is expressed as the presynaptic inhibitory action. In this study it was aimed to observe the inhibitory effect of imipramine caused by a single and chronic administration on both postsynaptic and presynaptic action of clonidine in pithed rats, and discussed in relation with the mechanism of antidepressant action of imipramine. 1) A rise of diastolic blood pressure by clonidine was not antagonized by prazosin, but by both phentolamine and piperoxan. 2) The inhibition by clonidine of tachycardia which was induced by electrical stimulation was also antagonized by phentolamine and piperoxan, but not by prazosin. 3) The increase in diastolic blood pressure in response to clonidine was inhibited by both a single or chronic administration with imipramine (20 mg/kg). It was more pronounced in the latter. 4) The inhibitory action of clonidine on the tachycardia was markedly inhibited by both types of administration with imipramine, between which there showed little difference. It is concluded that the presynaptic ${\alpha}_2-adrenoceptor$ is rather sensitively affected by a single administration with imipramine, and a long-term imipramine treatment may inhibit both pre- and postsynaptic ${\alpha}_2-adrenoceptors$, simultaneously. Furthermore, it was seemed unlikely that these results provide the evidence :to support the fact that the subsensitivity of presynaptic ${\alpha}_2-adrenoceptor$ may be the mechanism of action of tricyclic antidepressant.

• Korean Journal of Veterinary Service
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• v.25 no.1
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• pp.53-73
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• 2002

It has been reported that degranulation of mast cells in rats, rabbits and dog was observed after dosing xylazine hydrochloride(Xh) which has been widely used as sedative, analgesic and muscular relaxant. Therefore, this experiment was conducted to examine the relations between Xh and histamine release and to identify the action of ${\alpha}$-adrenoceptors which exists on the suface of mast cells. 1. The content of histamine within serum was measured with HPLC by performing the O-phthalaldehyde(OPA) fluorescent derivation. The pretreatment method had a little modification from the conventional method. The pretreament was carried out in the following method. 0.2$m\ell$ of serum and 1$m\ell$ of butanol were added to mixed together and then the liquid was centrifugally separated at 4$^{\circ}C$ and 2,000 rpm for 3 minutes. 0.4$m\ell$ of 0.1N HCl and 1.6$m\ell$ of heptane were added to 0.8$m\ell$ of supernatant taken from the liquid, and they were mixed together. This mixture was also centrifugally separated at 4$^{\circ}C$ and 2,000 rpm for 5 minutes. The supernatant was thrown away and the OPA fluorescent derivation was carried out with 0.2$m\ell$ of the lower liquid then, 5 minutes after mixing 400${\mu}\ell$ of 0.1N HCl, 120${\mu}\ell$ of 1N NaOH and 40${\mu}\ell$ of 0.1% OPA in the 0.2$m\ell$ of the lower liquid,120${\mu}\ell$ of 3.57N H$_3$PO$_4$ was added to the mixed liquid, and the liquid, was mixed again and syringe-filtered. Then, the measurement was done with HPLC in the 30 : 70(ν/ν) ratio of 0.004M KH$_2$PO$_4$: CH$_3$CN, flow rate of 1.0$m\ell$/min., and a wavelength of λex= 350nm and λem=444nm at the column temperature of 27$^{\circ}C$, using the fluorescence detector. 2. The content of histamine in each laboratory animal appeared to be higher in such an order as rabbit, rat, guinea pig, dog, Korean indigenous goat, swine, Korean indigenous cattle, Holstein, and mouse, of which the individual mean values${\pm}$standard deviation were 2.0668 ${\pm}$ 0.6049. 0.4999 ${\pm}$ 0.2278, 0.4241 ${\pm}$ 0.1974, 0.1054 ${\pm}$ 0.0556, 0.1028 ${\pm}$ 0.0276, 0.0972 ${\pm}$ 0.0513, 0.0872 ${\pm}$ 0.0373, 0.0717 ${\pm}$ 0.0379, and 0.0706 ${\pm}$ 0.0366, respectively. 3. The content of histamine was measured at the moments of 15-, 30-, 60-, 120-minutes after inoamuscular injection of 20mg/100kg Xh into two to 4 years old Holstein weighing 600∼700kg. The result showed that there was a significant increase at the times of 30- and 90-minutes after injection(p<0.05). 4. Intramuscular injection of 3mg/10kg Xh was given to crossbred pug dogs weighing 2.5∼4.3kg. The content of histamine was measured at the times of 30-, 60-, 90- and 120-minutes after injection. The result revealed that there was a significant increase at the times of 60-and 90-minutes after injection(p<0.05). 5. Intramuscular injection of 10mg/$m\ell$∼25mg/$m\ell$ Xh in concentration of 0.1$m\ell$ was applied to Korean indigenous goat over 5 months old. Then, the content of histamine was measured at the times of 15-, 30-, 60- and 90-minutes after injection. A significant increase was shown at the times of 30- and 60-minutes after injection(p<0.05). 6. The content of histamine was measured at the moments of 30- and 60-minutes after intramuscular injection of 0.1-0.2$m\ell$ Xh (20mg/$m\ell$) into male rabbits weighting 2.5-4kg. A significant increase was found at the moment of 60 minutes after injection(p<0.001). 7. After administering Xh to the mast cell taken from the abdominal cavity of mouse, the content of histamine was measured. The result showed that the higher the concentration, the more significantly the content of histamine was increased(p<0.05). 8. Compound 48/80 was administered in concentration of 5$\mu\textrm{g}$/$m\ell$ and 10$\mu\textrm{g}$/$m\ell$ to the mast cell picked from the abdominal cavity of mouse. The result showed that there was a significant increase in the content of histamine in case of the concentration of 10$\mu\textrm{g}$/$m\ell$(p<0.05). It was found to be about 10,000 to 500,000 times stronger than the Xh. 9. After premedication of 1mg/kg of yohimbine hydrochloride as ${\alpha}$$_2$-adrenergic antagonist to rabbits, the Xh was administered to them. The result was that the value of histamine within serum was decreased significantly(p<0.001). 10. After premeditation of 1mg/kg of prazosin hydrochloride as ${\alpha}$$_1$-adrenergic antagonist to rabbits, the Xh was administered to them. It was found that the value of histamine within serum was decreased significantly(p<0.005). 11, Prazosin hydrochloride and yohimbine hydrochloride as ${\alpha}$$_1$-adrenergic antagonist, respectively, and ${\alpha}$$_2$-adrenergic antagonist were administerd. In this case, the value of histamine within serum was decreased significantly(p<0.0001). As the results, when the Xh is administered to various kinds of animals, the amount of histamine release within serum is increased. In view of the results so far achieved, it is concluded that Xh acted on both a$_1$-adrenoreceptor and ${\alpha}$$_2$-adrenoreceptor induces the degranulation of mast cell.