• The Korean Journal of Pharmacology
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• v.27 no.1
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• pp.53-67
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• 1991

The characteristics and differences between DMPP and McN-A-343 on the secretory effect of catecholamines(CA) were studied in the isolated perfused rat adrenal glands. DMPP(100 uM) and McN-A-343(100 uM) perfused into an adrenal vein of the gland casued significant increases in CA secretion. On molar basis the secretory effect of McN-A-343 was about one fifth as potent as that of DMPP. Tachyphylaxis to releasing effects of CA evoked by DMPP and McN-A-343 was not observed by repeated perfusion of these agents. The DMPP-evoked CA secretion was significantly inhibited by pretreatment with chlorisondamine, desipramine and profusion of $Ca^{2+}-free$ Krebs solution containing EGTA, while it was not affected by pirenzepine, ouabain and physostigmine. However, pretreatment with atropine rather enhanced CA release by DMPP. The releasing effect of CA induced by McN-A-343 was markedly depressed by pretreatment with atropine, pirenzepine, chlorisondamine, physostigmine, and perfusion of $Ca^{2+}-free$ medium plus EGTA but was not influenced by desipramine, except for the case of ouabain which clearly potentiated CA release by McN-A-343. These experimental results suggest that both DMPP and McN-A-343 cause greatly secretion of CA from the isolated perfused rat adrenal glands by a calcium-dependent exocytotic mechanism. The secretory effect of DMPP is due to the stimulation of cholinergic nicotinic receptors and the secretion by McN-A-343 via activation of selecive $M_{1}-muscarinic$ receptors in the adrenal gland. It is also thought that the DMPP-evoked secretory effect is much greater than McN-A-343-induced effect.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.167-181
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• 1991

The present study was an attempt to investigate the effect of forskolin on secretion of catecholamines (CA) evoked by Ach, excess $K^+$, DMPP, McN-A-343 and caffeine from the isolated perfused rat adrenal glands and to elucidate its mechanism of action. The perfusion with forskolin (1.0 uM) for 1 min into the adrenal vein enhanced markedly the secreation of CA evoked by Ach (50 ug), excess $K^+$ (56 mM) DMPP (100 uM) and by caffeine (0.3 mM) but did not that by McN-A-343. Forskolin alone did not potentiate the CA secretion. Moreover, forskolin augmented the CA release evoked by the above same stimulation even in the absence of extracellular calcium. The 1 min perfusion of 300 uM-dibutyryl cyclic AMP (DBcAMP), which is known to increase cyclic AMP levels, led to enhancement of Ca secretion evoked by Ach, excess $K^+$ and DMPP but did not that by McN-A-343 and caffeine. DBcAMP by itself also did not augment the CA secretion. In the calcium-free medium DBcAMP significantly enhanced the CA secretion by the same stimulation, except for the case of McN-A-343. These experimental results suggest that forskolin activates adenylate cyclase, resulting the elevation of cyclic AMP which may potentiate cholinergic nicotinic receptor-mediated and also depolarization-dependent CA secretion and that it may alter the intracellular calcium homeostasis in the rat adrenal glands.

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.23-30
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• 1981

1) Effects of McN-A-343, clonidine and cocaine on the contractile response of the rat and rabbit vas deferens to field stimulation were investigated. The action mechanisms of these drugs have shown to be associated with endogenous norepinephrine(NE). 2) The contractile response to the stimulation of 5-10 Hz was markedly inhibited by the cumulative doses of McN-A-343 (0.003, 0.03, $0.3{\mu}g/ml$), clonidine (0.003, $0.3{\mu}g/ml$) and cocaine $(0.03\;{\mu}g/ml)$. The inhibition was antagonized by yohimbine and pjperoxan. 3) The inhibitory effect of McN-A-343 $(0.03{\mu}g/ml)$ and cocaine $(0.03{\mu}g/ml)$ was markedly enhanced by the same dose of cocaine and McN-A-343, respectively. This enhanced inhibition was also antagonized by yohimbine. 4) The contractile response to the stimulation of 0.01 Hz and 5-10 Hz was markedly potentiated by comparatively large doses of McN-A-343 $(30\;{\mu}g/ml)$ and $(3\;{\mu}g/ml)$. This potentiation was not observed in the presence of thymoxamine. The potentiation by McN-A-343 also did not appear in the presence of atropine. 5) The contractile response to the above stimulation was potentiated by muscarine and the potentiation was markedly attenuated in the presence of thymoxamine and atropine.

• The Korean Journal of Pharmacology
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• v.11 no.2
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• pp.29-40
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• 1975

1. Sites of the cardioaccelerating action of nicotine, DMPP, McN-A-343, AHR-602, tyramine, angiotensin and neostigmine were investigated in spinal rabbits. 2. The cardioaccelerating action of the above substances was substantially weak in reserpine-pretreated rabbits. The accelerating action was scarcely observed after propranolol administration. 3. Tetrodotoxin and guanethidine did not affect the cardioacceleration due to nicotine, DMPP, tyramine and isoproterenol, but they markedly weakened that due to McN-A-343, AHR-602, angiotensin and neostigmine. 4. Chlorisondamine blocked the cardioacceleration by nicotine and DMPP; atropine that by McN-A-343 and AHR-602. 5. Appropriate doses of isoproterenol, nicotine, DMPP, McN-A-343, tyramine, angiotensin and neostigmine, when administered into the right auricle, produced almost the same degree of cadia acceleration as when they were given to the right ear vein. AHR-602 did not produce significant cardioacceleration through this route. 6. Nicotine, DMPP and neostigmine when injected into the right auricle produced marked cardioacceleration, whereas they produced little action when injected into the left ventricle. Isoproterenol and tyramine produced more marked effect by the intraauricular route than the intraventricular one. 7. McN-A-343, AHR-602 and angiotensin produced more marked cardioacceleration by the intraventricular administration than the intraauricular one. The intraventricular AHR-602 produced marked cardioacceleration. 8. It is inferred that the sites of cardioaccelerating action of nicotine, DMPP, and tyramine will be either the terminals of the adrenergic nerves or the extraneuronal stores of norepinephrine and that of McN-A-343, AHR-602, angiotensin and neostigmine will be the adrenergic neurons in the heart. The sites on which nicotine, DMPP, tyramine and neostigmine will act are chiefly distributed in the auricular tissues and those on which McN-A-343, AHR-602, and angiotensin act chiefly in the ventricular tissues.

• The Korean Journal of Pharmacology
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• v.3 no.1
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• pp.15-18
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• 1967

Sympathetic ganglionic stimulants (DMPP, Wy-615, TMA and McN-A-343) produced pressor response in chickens anesthetized with phenobarbital sodium. In adrenalectomized chickens the pressor activity of DMPP, Wy -615 and TMA was less than in normal chickens but that of McN-A-343 was unchanged. Hexamethonium (20 mg/kg) and chlorisondamine (5 mg/kg), ganglionic blocking agents, reduced the pressor response to DMPP and Wy-615 but did not abolish the response. The pressor effect of McN-A-343 was not potentiated by the ganglionic flocking agents, but abolished by atropine.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1992.05a
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• pp.38-38
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• 1992

횐쥐 적출 완류부신을 이용하여 neuronal nicotinic(NN) agonist인 DMPP와 M1-muscarinic agonist인 McN-A-343의 카테콜아민(CA) 분비 작용의 차이와 특성에 대해서 연구한 결과는 다음과 같다. DMPP (100 $\mu$M)와 McN-A-343(100 $\mu$M)은 부신정맥내로 투여시 유의한 카테콜아민 분비작용을 나타내었다. Mol농도로 비교시 McN-A-343의 CA분비작용은 DMPP의 약 1/5정도였다. DMPP의 CA분비작용은 chlorisondamine이나 desipramine 또는 $Ca_2$$^{2}$-free Krebs ＋ EGTA 관류등의 전처치로 의의있게 억제되었으나, pirenzepine, ouabain 및 physostigmine등 전처치에 의해서는 영향을 받지않았다. 그러나 atropine 전처치시 DMPP의 분비작용은 오히려 증강되었다.

• The Korean Journal of Pharmacology
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• v.28 no.2
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• pp.171-179
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• 1992

Effects of a $M_1$ receptor antagonist, pirenzepine, a $M_2$ receptor antagonist, AF-DX116, and a nicotinic receptor antagonist, mecamylamine on the pressor responses to preganglionic sympathetic nerve stimulation (PNS) and McN-A-343 and DMPP in spinal (pithed) rabbits were investigated, in order to elucidate a functional role of $M_1$, $M_2$ and nicotinic receptors in ganglionic transmission. Pirenzepine and AF-DX116 selectively inhibited the McN-A-343-induced pressor response in chlorisondamine-treated rabbit and the BCh-induced bradycardia, respectively. Electrical stimulations of preganglionic sympathetic outflow at T8 level produced increases in blood pressure. Pirenzepine $(3\;{\mu}g/kg)$ significantly inhibited the PNS-induced pressor response and the degree of inhibition was not changed by increasing the doses to $100\;{\mu}g/kg$. AF-DX116 $(100\;{\mu}g/kg)$ had no effect on the PNS-induced pressor response. Mecamylamine inhibited the PNS-induced pressor response in a dose-dependent manner. The inhibitory action of mecamylamine was significantly augmented by combined-treatment with pirenzepine $(30\;{\mu}g/kg)$ but AF-DX116 $(100\;{\mu}g/kg)$ did not affect the inhibitory action of mecamylamine. McN-A-343 and DMPP elicited pressor response in the spinal rabbit. Pirenzepine and AF-DX116 dose-dependently inhibited the McN-A-343-induced pressor response but they did not affect DMPP-induced pressor response. Mecamylamine inhibited both pressor responses induced by McN-A-343 and DMPP. These results suggest that not only nicotinic receptors but also $M_1$ receptors play a facilitatory role in ganglionic transmission but $M_2$ receptors do not contribute the transmission in spinal (pithed) rabbits.

• Biomolecules & Therapeutics
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• v.10 no.3
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• pp.142-151
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• 2002

The present study was attempted to investigate the effect of apamin on catecholamine (CA) secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, cyclopiazonic acid and Bay-K-8644 from the isolated perfused rat adrenal gland and to establish the mechanism of its action. The perfusion of apamin (1 nM) into an adrenal vein for 20 min produced greatly potentiation in CA secretion evoked by ACh (5.32 $ imes$ $10^{-3}$ M), high $K^+$, (5.6 $ imes$ $10^{-2}$), DMPP ($10^{-4}$ M for 2 min), McN-A-343 ($10^{-4}$ M for 2 min), cyclopiazonic acid ($10^{-5}$ M for 4 min) and Bay-K-8644 ($10^{-5}$ M for 4 min). However, apamin itself did fail to affect basal catecholamine output. Furthermore, in adrenal glands preloaded with apamin (1 nM) under the presence of glibenclamide ($10^{-6}$ M), an antidiabetic sulfonylurea that has been shown to be a specific blocker of ATP-regulated potassium channels (for 20 min), CA secretion evoked by DMPP and McN-A-343 was not affected. However, the perfusion of high concentration of apamin (100 nM) into an adrenal vein for 20 min rather inhibited significantly CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, cyclopiazonic acid and Bay-K-8644. Taken together, these results suggest that the low concentration of apamin causes greatly the enhancement of CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization. These findings suggests that apamin-sensitive SK ($Ca^{2+}$) channels located in rat adrenal medullary chromaffin cells may play an inhibitory role in the release of catecholamines mediated by stimulation of cholinergic nicotinic and muscarinic receptors as well as membrane depolarization. However, it is thought that high concentration of apamin cause the inhibitory responses in catecholamine secretion evoked by stimulation of cholinergic receptors as well as by membrane depolarization from the rat adrenal gland without relevance with the SK channel blockade.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.297-297
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• 1994

It has been known that adrenal corticosteroids influence the expression of adrenomedullary catecholamine-synthetizing enzymes and also suppress the emission of axonal-like processes in cultured chromaffin cells. In the present study, it was attempted ta investigate the effect of 17${\alpha}$-estradiol on catecholamine(CA) secretion evoked by acetylcholine(ACh), DMPP, McN-A-343, excess K$\^$+/ and Bay-K-8644 from the isolated perfused rat adrenal gland. The perfusion of 17${\alpha}$-estradiol (10$\^$-6/ 10$\^$-4/M) me an adrenal vein for 20min produced relatively dose-dependent inhibition in CA secretion evoked by ACh (5.5 ${\times}$ 10$\^$-3/M), DMPP (10$\^$-4/M for 2min), McN-A-343 (10$\^$-4/M for 4min) and Bay-K-8644 (10$\^$-5/M for 4min), while did not affect the CA secretory effect of high K$\^$+/(5.6 x 10$\^$-2/M). Also, in the presence of 17${\beta}$-estradiol, CA secretion of ACh, DMPP and McN-A-343 without any effect on excess K$\^$+/-evoked CA secretion. However, in adrenal glands preloaded with 17${\alpha}$-estradiol (10$\^$-5/M) plus tamoxifen (10$\^$-5/M), which is known to be a selective antagonist of estrogen receptors (for 20min), CA secretory responses evoked by ACh, DMPP and McN-A-343 were considerably recovered as compared to that of 17${\alpha}$-estradiol only, but excess K$\^$+/-induced CA secretion was not affected.

• Biomolecules & Therapeutics
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• v.8 no.4
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• pp.338-348
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• 2000

The present study was attempted to determine the effect of 5'-(N'-ethylcarboxamido) adenosine (NECA), which is an potent $A_2$-adenosine receptor agonist, on catecholamine (CA) secretion evoked by cholinergic stimulation, membrane depolarization and calcium mobilization from the isolated perfused rat adrenal gland. NECA (20 nM) perfused into the adrenal vein for 60 min produced a time-related inhibition in CA secretion evoked by ACh (5.32x10$^{-3}$ M), high $K^{+}$(5.6x10$^{-2}$ M), DMPP (10$^{-4}$ M for 2 min), McN-A-343 (10$^{-4}$ M for 2 min), cyclopiazonic acid (10$^{-5}$ M for 4 min) and Bay-K-8644 (10$^{-5}$ M for 4 min). Also, in the presence of $\beta$,${\gamma}$-methylene adenosine-5'-triphosphate (MATP), which is also known to be a selective $P_{2x}$-purinergic receptor agonist, showed a similar inhibition elf CA release evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid. However, in adrenal glands preloaded with 20$\mu$M NECA for 20 min under the presence of 20$\mu$M 3-isobutyl-1-methyl-xanthine (IBMX), an adenosine receptors antagonist, CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were much recovered in comparison to the case of NECA-treatment only. Taken together, these results indicate that NECA causes the marked inhibition of CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization. This inhibitory effect may be mediated by inhibiting influx of extracellular calcium and release in intracellular calcium in the rat adrenomedullary chromaffin cells through the adenosine receptor stimulation. Therefore, it is suggested that the inhibitory mechanism of adenosine receptor stimulation may play a modulatory role in regulating CA secretion.n.n.