In this study, effects of the intraventricular and intravenous dimethylphenylpiperazinium (DMPP) on the renal function of rabbits were investigated. Intraventricular DMPP (100 microgram) elicited diuresis following antidiuresis concomitant with the changes in renal blood flow, glomerular filtration rate and urinary excretory amount of electrolytes (Na and K). The changes in urine flow correlated with the changes in renal blood flow, glomerular filtration rate and excretory rates of electrolytes in urine. Intravenous DMPP (50 microgram/kg) did not affect the renal function.
Dimethylphenylpiperazinium Iodide ; Diuresis ; Electrolytes ; Glomerular Filtration Rate ; Rabbits* ; Renal Circulation

The Effects of Some Autonomic Drugs on the Elevated Intraocular Tension of the Rabbit were Investigated. 1) Intravenous or local administration of Acetylcholine isoproterenol, a small dose of epinephrine and local large dose of epinephrine shortened the recovery time of the elevated. intraocular tension of normal level. 2) Intravenous or local administration of norepinephrine and intravenous large dose of epinephrine lengthened the recovery time. 3) A small dose of intravenous dimethylphenylpiperazinium shortened the recovery time, while large dose of the former lengthened the latter. 4) Intravenous hexamethonium, Bretylium, regitine, and small dose of atropine lengthened it From the above results, it is suggested that there are cholinergic, adrenergic alpha and beta receptor in the regulatory organs of the intraocular tension and autonomic nervous system plays an important role in regulating the intraocular tension.
Acetylcholine ; Atropine ; Autonomic Agents* ; Autonomic Nervous System ; Dimethylphenylpiperazinium Iodide ; Epinephrine ; Hexamethonium ; Isoproterenol ; Norepinephrine ; Phentolamine

Effects of a M1 receptor antagonist, pirenzepine, a M2 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 M1, M2 and nicotinic receptors in ganglionic transmission. Pirenzepine and AF-DX116 selectively inhibited the McN-A-343-induced pressor reponse 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 microgram/kg) significantly inhibited the PNS-induced pressor response and the degree of inhibition was not changed by increasing the doses to 100 microgram/kg. AF-DX116(100 microgram/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 microgram/kg) but AF-DX116(100 microgram/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 Mc-N-343- and DMPP. These results suggest that not only nicotinic receptors but also M1 receptors play a facilitatory role in ganglionic transmission but M2 receptors do not contribute the transmission in spinal(pithed) rabbits.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride ; Blood Pressure ; Bradycardia ; Dimethylphenylpiperazinium Iodide ; Electric Stimulation ; Ganglia, Sympathetic* ; Ganglion Cysts ; Mecamylamine ; Pirenzepine ; Rabbits ; Receptors, Nicotinic*

Melatonin is a neurotransmitter that modulates various physiological phenomena including regulation and maintenance of the circadian rhythm. Nicotinic acetylcholine receptors (nAChRs) play an important role in oral functions including orofacial muscle contraction, salivary secretion, and tooth development. However, knowledge regarding physiological crosstalk between melatonin and nAChRs is limited. In the present study, the melatonin-mediated modulation of nAChR functions using bovine adrenal chromaffin cells, a representative model for the study of nAChRs, was investigated. Melatonin inhibited the nicotinic agonist dimethylphenylpiperazinium (DMPP) iodide-induced cytosolic free Ca²⁺ concentration ([Ca²⁺](i)) increase and norepinephrine secretion in a concentration-dependent manner. The inhibitory effect of melatonin on the DMPP-induced [Ca²⁺](i) increase was observed when the melatonin treatment was performed simultaneously with DMPP. The results indicate that melatonin inhibits nAChR functions in both peripheral and central nervous systems.
Calcium Signaling ; Central Nervous System ; Chromaffin Cells ; Circadian Rhythm ; Cytosol ; Dimethylphenylpiperazinium Iodide ; Melatonin ; Muscle Contraction ; Neurotransmitter Agents ; Nicotinic Agonists ; Norepinephrine ; Physiological Phenomena ; Receptors, Nicotinic ; Tooth

The present study was attempted to investigate the effect of strychnine on catecholamine (CA) secretion evoked by ACh, high K+, DMPP and McN-A-343 from the isolated perfused rat adrenal gland. The perfusion of strychnine (10-4 M) into an adrenal vein for 20 min produced great inhibition in CA secretory responses evoked by ACh (5.32X10-3 M), DMPP (10-4 M for 2 min) and McN-A-343 (10-4 M for 2 min), but did not alter CA secretion by high K+ (5.6X10-2 M). Strychnine itself did also fail to affect basal catecholamine output. Furthermore, in adrenal glands preloaded simultaneously with strychnine (10-4 M) and glycine (an agonist of glycinergic receptor, 10-4 M), CA secretory responses evoked by ACh, DMPP and McN-A-343 were considerably recovered to some extent when compared with those evoked by treatment with strychnine only. However, CA secretion by high K+ (5.6X10-2 M) was not affected. Taken together, these results demonstrate that strychnine inhibits greatly the CA secretory responses evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors, but does not affect that by membrane depolarization. It is suggested that strychnine-sensitive glycinergic receptors are localized in rat adrenal medullary chromaffin cells.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride ; Adrenal Glands* ; Animals ; Chromaffin Cells ; Dimethylphenylpiperazinium Iodide ; Glycine ; Membranes ; Perfusion ; Rats* ; Receptors, Cholinergic* ; Strychnine* ; Veins

The effects of presynaptic nicotinic acetylcholine receptors (nAChRs) on excitatory synaptic transmission in CA1 pyramidal neurons of the rat hippocampus were examined by blind whole-cell patch clamp recording from hippocampal slice preparations. Local application of the nAChRs agonist dimethylphenyl-piperazinium iodide (DMPP) did not induce a postsynaptic current response in CA1 pyramidal cells. However, DMPP enhanced the frequency and amplitude of spontaneous excitatory postsynaptic current (sEPSC) in these cells in a dose-dependent manner. This enhancement was blocked by the selective nicotinic alpha-7 receptor antagonist alpha-bungarotoxin, but not by the antagonist mecamylamine, hexamethonium or dihydro-beta-erythroidine. The frequency of miniature excitatory postsynaptic current (mEPSC) in CA1 pyramidal neurons was also increased by application of DMPP, indicating a presynaptic site of action of the agonist. Taken together, these results suggest that activation of presynaptic nAChRs in CA1 pyramidal neurons, which contain alpha-7 subunits, potentiates presynaptic glutamate release and consequently modulate excitatory synaptic transmission in the hippocampus.
Animals ; Bungarotoxins ; physiology ; Dimethylphenylpiperazinium Iodide ; pharmacology ; Glutamic Acid ; pharmacology ; Hippocampus ; physiology ; Male ; Neurons ; physiology ; Nicotinic Agonists ; pharmacology ; Pacemaker, Artificial ; Patch-Clamp Techniques ; Rats ; Rats, Wistar ; Receptors, Nicotinic ; physiology ; Receptors, Presynaptic ; physiology ; Synapses ; physiology ; Synaptic Transmission ; alpha7 Nicotinic Acetylcholine Receptor

The aim of the present study was to investigate the effects of R-(-)-2,10,11-trihydroxy-N-propylnoraporphine [R-(-)-TNPA], a selective agonist of dopaminergic D2 receptor and S(-)-raclopride, a selective antagonist of dopaminergic D2 receptor, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused model of the rat adrenal gland, and also to establish its mechanism of action. R-(-)-TNPA (10~100 micrometer) perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretory responses evoked by ACh (5.32 mM), high K+ (56 mM), DMPP (100 micrometer) and McN-A-343 (100 micrometer). R-(-)-TNPA itself did also fail to affect basal CA output. Also, in adrenal glands loaded with R-(-)-TNPA (30 micrometer), the CA secretory responses evoked by Bay-K-8644 (10 micrometer), an activator of L-type Ca2+ channels and cyclopiazonic acid (10 micrometer), an inhibitor of cytoplasmic Ca2+-ATPase were also inhibited. However, S(-)-raclopride (1~10 micrometer), given into an adrenal vein for 60 min, enhanced the CA secretory responses evoked by ACh, high K+, DMPP and McN-A-343 only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, S(-)-raclopride (3.0 micrometer) in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644 and cyclopiazonic acid only for the first period (4 min). However, after simultaneous perfusion of R-(-)-TNPA (30 micrometer) and S(-)-raclopride (3.0 micrometer), the inhibitory responses of R-(-)-TNPA (30 micrometer) on the CA secretion evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644, and cyclopiazonic acid were significantly reduced. Taken together, these experimental results suggest that R-(-)-TNPA greatly inhibits the CA secretion from the perfused rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization, but S(-)-raclopride rather enhances the CA release by them. It seems that this inhibitory of R-(-)-TNPA may be mediated by stimulation of inhibitory dopaminergic D2 receptors located on the rat adrenomedullary chromaffin cells, while the facilitatory effect of S(-)-raclopride is due to the blockade of dopaminergic D2 receptors, which are relevant to extra- and intracellular calcium mobilization. Therefore, it is thought that dopaminergic D2 receptors may be involved in regulation of CA release in the rat adrenal medulla.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride ; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; Adrenal Glands ; Adrenal Medulla* ; Animals ; Calcium ; Catecholamines ; Chromaffin Cells ; Cytoplasm ; Dimethylphenylpiperazinium Iodide ; Membranes ; Perfusion ; Rats* ; Veins

The aim of the present study was to investigate whether ginsenoside-Rb2 (Rb2) can affect the secretion of catecholamines (CA) in the perfused model of the rat adrenal medulla. Rb2 (3~30 microM), perfused into an adrenal vein for 90 min, inhibited ACh (5.32 mM)-evoked CA secretory response in a dose- and time-dependent fashion. Rb2 (10 microM) also time-dependently inhibited the CA secretion evoked by DMPP (100 microM, a selective neuronal nicotinic receptor agonist) and high K+ (56 mM, a direct membrane depolarizer). Rb2 itself did not affect basal CA secretion (data not shown). Also, in the presence of Rb2 (50 microg/mL), the secretory responses of CA evoked by veratridine (a selective Na+ channel activator (50 microM), Bay-K-8644 (an L-type dihydropyridine Ca2+ channel activator, 10 microM), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor, 10 microM) were significantly reduced, respectively. Interestingly, in the simultaneous presence of Rb2 (10 microM) and L-NAME (an inhibitor of NO synthase, 30 microM), the inhibitory responses of Rb2 on ACh-evoked CA secretory response was considerably recovered to the extent of the corresponding control secretion compared with the inhibitory effect of Rb2-treatment alone. Practically, the level of NO released from adrenal medulla after the treatment of Rb2 (10 microM) was greatly elevated compared to the corresponding basal released level. Collectively, these results demonstrate that Rb2 inhibits the CA secretory responses evoked by nicotinic stimulation as well as by direct membrane-depolarization from the isolated perfused rat adrenal medulla. It seems that this inhibitory effect of Rb2 is mediated by inhibiting both the influx of Ca2+ and Na+ into the adrenomedullary chromaffin cells and also by suppressing the release of Ca2+ from the cytoplasmic calcium store, at least partly through the increased NO production due to the activation of nitric oxide synthase, which is relevant to neuronal nicotinic receptor blockade.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; Adrenal Medulla ; Animals ; Calcium ; Catecholamines ; Chromaffin Cells ; Cytoplasm ; Dimethylphenylpiperazinium Iodide ; Membranes ; Neurons ; NG-Nitroarginine Methyl Ester ; Nitric Oxide Synthase ; Rats ; Receptors, Nicotinic ; Veins ; Veratridine

The aim of the present study was designed to establish comparatively the inhibitory effects of D1-like and D2-like dopaminergic receptor agonists, SKF81297 and R(-)-TNPA on the release of catecholamines (CA) evoked by cholinergic stimulation and membrane depolarization from the isolated perfused model of the rat adrenal medulla. SKF81297 (30 micrometer) and R-(-)-TNPA (30 micrometer) perfused into an adrenal vein for 60 min, produced great inhibition in the CA secretory responses evoked by ACh (5.32x10(-3) M), DMPP (10(-4) M), McN-A-343 (10(-4) M), high K+ (5.6x10(-2) M), Bay-K-8644 (10 micrometer), and cyclopiazonic acid (10 micrometer), respectively. For the release of CA evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid, the following rank order of inhibitory potency was obtained: SKF81297>R-(-)-TNPA. However, R(+)-SCH23390, a selectve D1-like dopaminergic receptor antagonist, and S(-)-raclopride, a selectve D2-like dopaminergic receptor antagonist, enhanced the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid only for 0~4 min. The rank order for the enhancement of CA release evoked by high K+, McN-A-343 and cyclopiazonic acid was R(+)-SCH23390>S(-)-raclopride. Also, the rank order for ACh, DMPP and Bay-K-8644 was S(-)-raclopride > R(+)-SCH23390. Taken together, these results demonstrate that both SKF81297 and R-(-)-TNPA inhibit the CA release evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors and the membrane depolarization from the isolated perfused rat adrenal gland without affecting the basal release, respectively, but both R(+)-SCH23390 and S(-)-raclopride facilitate the CA release evoked by them. It seems likely that the inhibitory effects of SKF81297 and R-(-)-TNPA are mediated by the activation of D1-like and D2-like dopaminergic receptors located on the rat adrenomedullary chromaffin cells, respectively, whereas the facilitatory effects of R(+)-SCH23390 and S(-)-raclopride are mediated by the blockade of D1-like and D2-like dopaminergic receptors, respectively: this action is possibly associated with extra- and intracellular calcium mobilization. Based on these results, it is thought that the presence of dopaminergic D1 receptors may play an important role in regulation of the rat adrenomedullary CA secretion, in addition to well-known dopaminergic D2 receptors.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride ; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; Adrenal Glands ; Adrenal Medulla ; Animals ; Benzazepines ; Calcium ; Catecholamines ; Chromaffin Cells ; Dimethylphenylpiperazinium Iodide ; Indoles ; Membranes ; Rats ; Veins

The aim of the present study was to investigate the effects of 6-chloro-7,8-dihydroxy-1-phenyl-2,3, 4,5-tetrahydro-1H-3-benzazepine (SKF81297), a selective agonist of dopaminergic D1 receptor, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused rat adrenal gland, and also to elucidate the mechanism involved. SKF81297 (10~100microM) perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition of CA secretory responses evoked by ACh (5.32 mM), high K+ (56 mM), DMPP (100microM) and McN-A-343 (100microM). Also, in adrenal glands loaded with SKF81297 (30microM), the CA secretory responses evoked by Bay-K-8644 (10microM), an activator of L-type Ca2+ channels and cyclopiazonic acid (10microM), an inhibitor of cytoplasmic Ca2+-ATPase were also inhibited. However, in the presence of the dopamine D1 receptor antagonist, (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-benzazepine-7-ol (SCH23390, 3microM), which is a selective antagonist of dopaminergic D1 receptor, the inhibitory responses of SKF81297 (30microM) on the CA secretion evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644, and cyclopiazonic acid were significantly reduced. Collectively, these experimental results suggest that SKF81297 inhibits the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization. This inhibitory of SKF81297 seems to be mediated by stimulation of dopaminergic D1 receptors located on the rat adrenomedullary chromaffin cells, which are relevant to extra- and intracellular calcium mobilization. Therefore, it is thought that the presence of the dopaminergic D1 receptors may be involved in regulation of CA release in the rat adrenal medulla.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride ; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; Adrenal Glands ; Adrenal Medulla* ; Animals ; Calcium ; Catecholamines ; Chromaffin Cells ; Cytoplasm ; Dimethylphenylpiperazinium Iodide ; Membranes ; Rats* ; Receptors, Dopamine D1 ; Veins