1.Role of histamine H(1) and H(2) receptors in the modulation of respiratory rhythmical discharge in medulla oblongata slice preparation of neonatal rats.
Ying QI ; Zhi-Bin QIAN ; Zhong-Hai WU
Acta Physiologica Sinica 2008;60(3):397-402
The present study was carried out to determine the role of histamine H(1) and H(2) receptors in the generation of basic respiratory rhythm. Neonatal (aged 0-3 d) Sprague-Dawley rats of either sex were used. The medulla oblongata slice containing the medial region of the nucleus retrofacialis (mNRF) and the hypoglossal nerve rootlets was prepared and the surgical procedure was performed in the modified Kreb's solution (MKS) with continuous carbogen (95% O(2) and 5% CO(2)), and ended in 3 min. Respiratory rhythmical discharge activity (RRDA) of the rootlets of hypoglossal nerve was recorded by suction electrode. Thirty medulla oblongata slice preparations were divided into 5 groups. In groups I, II and III, histamine (5 μmol/L), H(1) receptor specific antagonist pyrilamine (10 μmol/L) and H(2) receptor specific antagonist cimetidine (5 μmol/L) was added into the perfusion solution for 15 min separately. In group IV, after application of histamine for 15 min, additional pyrilamine was added into the perfusion for another 15 min. In group V, after application of histamine for 15 min, additional cimetidine was added into the perfusion for another 15 min. The discharges of the roots of hypoglossal nerve were recorded. Signals were amplified and band-pass filtered (100-3.3 kHz). Data were sampled (1-10 kHz) and stored in the computer via BL-420 biological signal processing system. Our results showed that histamine significantly decreased the respiratory cycle (RC) and expiratory time (TE), but changes of integral amplitude (IA) and inspiratory time (TI) were not statistically significant. Pyrilamine induced significant increases in RC and TE, but changes of TI and IA were not statistically significant. Cimetidine had no effects on RC, TE, TI and IA of RRDA. The effect of histamine on the respiratory rhythm was reversed by additional application of pyrilamine but not cimetidine. Taken together, with the results mentioned above, histamine H(1) receptors but not H(2) receptors may play an important role in the modulation of RRDA in the medulla oblongata slice preparation of neonatal rats.
Animals
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Animals, Newborn
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Cimetidine
;
pharmacology
;
Female
;
Histamine
;
pharmacology
;
Histamine H1 Antagonists
;
pharmacology
;
Histamine H2 Antagonists
;
pharmacology
;
Hypoglossal Nerve
;
physiology
;
In Vitro Techniques
;
Male
;
Medulla Oblongata
;
physiology
;
Pyrilamine
;
pharmacology
;
Rats
;
Rats, Sprague-Dawley
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Receptors, Histamine H1
;
physiology
;
Receptors, Histamine H2
;
physiology
;
Respiration
2.Roles of the histaminergic receptors in the locus ceruleus in stress-induced carotid baroreflex resetting in rats.
Guo-qing WANG ; Jian-xiang LI ; Chun-ling FU ; Wan-ping SUN ; Jian TONG
Chinese Journal of Applied Physiology 2007;23(2):168-172
AIMTo explore the roles of H1 and H2 receptors in the locus ceruleus (LC) in the carotid baroreflex (CBR) resetting resulted from foot-shock stress.
METHODSMale SD rats were divided into two groups (n=18) at random: unstressed and stressed group. The latter were subjected to unavoidable electric foot-shock twice daily for a week and each session of foot-shock lasted 2 hours. The left and right carotid sinus regions were isolated from the systemic circulation in all animals anesthetized with pentobarbital sodium. The intracarotid sinus pressure (ISP) was altered in a stepwise manner in vivo. ISP-mean arterial pressure (MAP), ISP-Gain relationship curves and reflex characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CBR performance induced by stress and the effects of microinjection with histaminergic receptors antagonists into the LC on the responses of CBR to stress were examined.
RESULTSStress significantly shifted the ISP-MAP relationship curve upwards (P < 0.05) and obviously moved the middle part of ISP-Gain relationship curve downwards (P < 0.05), and decreased the value of the MAP range and maximum gain (P < 0.05), but increased the threshold pressure, saturation pressure, set point and ISP at maximum gain (P < 0.05). Microinjection of selective H1 or H2 receptor antagonist, chlorpheniramine (CHL, 0.5 microg/microl) or cimetidine (CIM, 1.5 microg/microl) into the LC, significantly attenuated the above-mentioned changes in CBR performance induced by stress and the alleviate effect of CIM was less remarkable than that of CHL (P < 0.05). The responses of CBR under stress to H1 or H2 receptor antagonist generally occurred 20 min after the administration and lasted approximately for 16 min. Microinjection with the same dose of CHL or CIM into the LC in the unstressed group did not change CBR performance significantly (P > 0.05). However, microinjection of CHL or CIM into the LC could not completely abolish the stress-induced changes in CBR.
CONCLUSIONThe stress results in a resetting of CBR and a decrease in reflex sensitivity. The stress-induced changes in CBR may be mediated, at least in part, by activating the brain histaminergic system. The H1 and H2 receptors in the LC, especially, Hi receptors may play an important role in the resetting of CBR under stress. The descending histaminergic pathway from the hypothalamus to LC may be involved in these effects. Moreover, the effects of stress on CBR also have other mechanisms.
Animals ; Baroreflex ; Carotid Sinus ; physiology ; Locus Coeruleus ; physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H1 ; physiology ; Receptors, Histamine H2 ; physiology ; Stress, Physiological
3.Effect of histamine on intracortical blood vessels of rats.
Jian-jun ZHAO ; Yong LIU ; Xin-lin CHEN ; Jian-xin LIU ; Ying-fang TIAN ; Peng-bo ZHANG ; Qian-yan KANG ; Fen QIU ; Peng-bo YANG
Journal of Southern Medical University 2006;26(9):1284-1287
OBJECTIVETo investigate histamine-induced changes of the intracortical vessels in the cortical slice of rat brain.
METHODSImmunohistochemistry was employed to detect the expression of H1 and H2 receptors in the intracortical blood vessels of rats. Histamine-induced constriction of the intracortical blood vessels of the brain slices was observed with differential interference contrast microscope. Measurements of the luminal diameter were made on-line during the course of the experiment and confirmed off-line from the stored images. In order to observe whether histamine H1 and H2 receptors affected histamine-induced constriction, the intracortical blood vessels in the brain slices were pre-treated with H1 receptor antagonist diphenhydramine and H2 receptor antagonist cimetidine.
RESULTSExpression of H1 and H2 receptors was detected in the intracortical blood vessels of the rat brain. Histamine (1-100 micromol/L) induced a concentration-dependent constriction from (1.48-/+0.67)% to (32.91-/+7.91)%. The reactions to each histamine concentration were significantly (P<0.01) different from each other, with the exception of the highest histamine concentrations (30 and 100 micromol/L) when maximal constriction due to histamine were observed (P>0.05). With pre-treatment of the slice with 10 micromol/L diphenhydramine, application of histamine did not elicit constriction. Pre-treatment of the slice with 10 micromol/L cimetidine did not completely inhibit but somehow significantly weakened vascular constriction in response to histamine treatment at 10 and 30 micromol/L (P<0.05).
CONCLUSIONHistamine can induce constriction of the intracortical blood vessels, which is mediated by H1 receptor.
Animals ; Blood Vessels ; drug effects ; metabolism ; physiology ; Cerebral Cortex ; blood supply ; Cimetidine ; pharmacology ; Diphenhydramine ; pharmacology ; Histamine ; pharmacology ; Histamine H1 Antagonists ; pharmacology ; Histamine H2 Antagonists ; pharmacology ; In Vitro Techniques ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H1 ; metabolism ; physiology ; Receptors, Histamine H2 ; metabolism ; physiology ; Vasoconstriction ; drug effects
4.Effect of alahistidine on brain histamine content and seizure development.
Wei-wei HU ; Zhong CHEN ; Li-sha XU ; Chun-lei JIN ; Eiko SAKURAI ; Kazuhiko YANAI
Journal of Zhejiang University. Medical sciences 2004;33(3):197-200
OBJECTIVETo investigate the effect of alahistidine on brain histamine content and seizure development.
METHODSThe kindling seizure was induced by ip injection with subconvulsant dose of pentylenetetrazole every 48 h. Monoamines and their metabolites were measured using a HPLC system and fluorometric assay.
RESULTChronic low histamine feeding markedly decreased histamine content in cortex and hypothalamus, and promoted seizure development induced by pentylenetetrazole. However, alahistidine feed reversed the decreased histamine content and slowed seizure development caused by low histamine feed. Both low histamine and alahistidine feed had no effect on norepinephrine, dopamine and its metabolites.
CONCLUSIONAlahistidine may affect histaminergic system and seizure development.
Animals ; Brain Chemistry ; drug effects ; Carnosine ; analogs & derivatives ; pharmacology ; Histamine ; analysis ; Male ; Pentylenetetrazole ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H1 ; physiology ; Seizures ; chemically induced
5.Histamine H1 receptors modulate the discharge activities of inspiratory neurons in the medial region of neonatal rat nucleus retrofacialis ex vivo.
Zhi-bin QIAN ; Ying QI ; Zhong-hai WU
Journal of Southern Medical University 2010;30(1):54-56
OBJECTIVETo investigate the role of histamine H1 receptors in modulating the discharge activities of the inspiratory neurons in the nucleus retrofacialis of neonatal rats.
METHODSBrainstem slices were obtained from neonatal rats containing the medial region of the nucleus retrofacialis (mNRF) with the hypoglossal nerve (XII nerve) rootlets retained. The rhythmic discharges of the inspiratory neurons (I neurons) and activities of the XII nerve rootlets were simultaneously recorded using microelectrodes and suction electrodes, respectively. The role of H1 receptors in modulation of the discharge activities of the inspiratory neurons was investigated using the H1 receptor agonist histamine and its specific antagonist pyrilamine dissolved in modified Kreb's solution for slice perfusion.
RESULTSHistamine shortened the respiratory cycle (RC) and expiratory time (TE) of the neurons in the brain slices, and pyrilamine produced the opposite effects. Neither histamine nor pyrilamine affected the inspiratory time (TI), integral amplitude (IA) or the peak discharge frequency (PF) of the I neurons.
CONCLUSIONH1 receptors play an excitatory role in the modulation of the discharge activities of the inspiratory neurons in neonatal rat brainstem slices.
Animals ; Animals, Newborn ; Electrophysiological Phenomena ; Female ; In Vitro Techniques ; Inhalation ; physiology ; Male ; Medulla Oblongata ; cytology ; physiology ; Neurons ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H1 ; physiology
6.Reversing effect of histamine on neuron death induced by N-methyl-D-aspartate.
Hai-bin DAI ; Zhong CHEN ; Yu-wen HUANG ; Qiu-fu GE ; Zhong-miao ZHANG ; Er-qing WEI
Journal of Zhejiang University. Medical sciences 2004;33(3):189-192
OBJECTIVETo determine the effect of histamine on N-methyl-D-aspartate (NMDA) induced neuron death and to elucidate its mechanism.
METHODSThe primary cortical cell culture was adopted. Neuron morphology and MTT assay were used to evaluate the drugs effects.
RESULTHistamine at doses of 10(-4) 10(-6) 10(-7) 10(-8) mol/L reversed the neuron death induced by NMDA (50 micromol/L) for 3 h. The protection of histamine peaked at doses of 10(-4) mol/L and 10(-7)mol/L. The effect of histamine of 10(-7) mol/L was reversed only by cimetidine an H(2)receptor antagonist. However, the effect of histamine of 10(-4) mol/L was reversed only by pyrilamine but not cimetidine.
CONCLUSIONHistamine could reduce neuron death induced by NMDA; its protection at a low dose might be mediated by H(2)receptor, and at a high dose by H(1)receptor.
Animals ; Cell Death ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Histamine ; pharmacology ; N-Methylaspartate ; toxicity ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H1 ; physiology ; Receptors, Histamine H2 ; physiology
7.The role of H1- and H2-receptors in the effect of compound 48/80 in the asphyxiation and body temperature of mice.
Ahmet ULUGOL ; Hakan KARADAG ; Dikmen DOKMECI ; Ismet DOKMECI
Yonsei Medical Journal 1996;37(2):97-103
Contribution of histamine H1- and H2-receptors to the effect of compound 48/80, a potent histamine releaser, upon asphyxiation and body temperature in mice was investigated in the present experiments. Compound 48/80 showed an apparent protective potency against hypoxia and significantly prolonged the latencies for convulsions and death in a dose-dependent manner. Compound 48/80 also decreased the body temperature, which was in relation with the antihypoxic effect. Both the H1-receptor antagonist, dimethindene, and the H2-receptor antagonist, ranitidine, attenuated the hypothermic effect of compound 48/80, indicating the involvement of central histamine through both the H1- and H2-receptors. Ranitidine had no effect on the protective effect of compound 48/80 against hypoxia-induced lethality, whereas dimethindene completely antagonized it. These results suggest that the protective effect of compound 48/80 against hypoxia is mediated through histamine H1-receptors and is not related to its ability to induce hypothermia.
Animal
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Anoxia/*drug therapy/physiopathology
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Body Temperature/*drug effects
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Convulsions/prevention & control
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Male
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Mice
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Mice, Inbred BALB C
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Receptors, Histamine H1/*physiology
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Receptors, Histamine H2/*physiology
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p-Methoxy-N-methylphenethylamine/*pharmacology
8.Mechanisms of histamine ameliorating memory impairment induced by pentylenetetrazole-kindling epilepsy in rats.
Lisan ZHANG ; Guanfeng CHEN ; Jiefang CHEN ; Xudong HE ; Xingyue HU
Journal of Zhejiang University. Medical sciences 2017;46(1):1-6
To investigate the effects of neuronal histamine on spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and to explore its mechanisms.A subconvulsive dose of pentylenetetrazole (35 mg/kg) was intraperitoneally injected in rats every 48 h to induce chemical kindling until fully kindled. Morris water maze was used to measure the spatial memory acquisition of the rats one week after fully pentylenetetrazole-kindled, and the histamine contents in different brain areas were measured spectrofluorometrically. Different dosages of hitidine (the precursor of histamine), pyrilamine (H1 receptor antagonist), and zolantidine (H2 receptor antagonist) were intraperitoneally injected, and their effects on spatial memory acquisition of the rats were observed.Compared with control group, escape latencies were significantly prolonged on Morris water maze training day 2 and day 3 in pentylenetetrazole-kindling epilepsy rats (all<0.05); and the histamine contents in hippocampus, thalamus and hypothalamus were decreased significantly (all<0.05). Escape latencies were markedly shortened on day 3 by intraperitoneally injected with histidine 500 mg/kg, and on day 2 and day 3 by intraperitoneally injected with histidine 1000 mg/kg in pentylenetetrazole-kindling epilepsy rats (all<0.05). The protection of histidine was reversed by zolantidine (10 and 20 mg/kg), but not by pyrilamine.Neuronal histamine can improve the spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and the activation of H2 receptors is possibly involved in the protective effects of histamine.
Animals
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Benzothiazoles
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pharmacology
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Brain Chemistry
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drug effects
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Epilepsy
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chemically induced
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complications
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Hippocampus
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chemistry
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Histamine H1 Antagonists
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pharmacology
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Histamine H2 Antagonists
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pharmacology
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Histidine
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pharmacology
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Hypothalamus
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chemistry
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Kindling, Neurologic
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physiology
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Memory Disorders
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drug therapy
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etiology
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Pentylenetetrazole
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Phenoxypropanolamines
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pharmacology
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Piperidines
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pharmacology
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Pyrilamine
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pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Histamine H2
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drug effects
;
physiology
;
Spatial Memory
;
drug effects
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Spectrometry, Fluorescence
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Thalamus
;
chemistry
9.Cyproheptadine Regulates Pyramidal Neuron Excitability in Mouse Medial Prefrontal Cortex.
Yan-Lin HE ; Kai WANG ; Qian-Ru ZHAO ; Yan-Ai MEI
Neuroscience Bulletin 2018;34(5):759-768
Cyproheptadine (CPH), a first-generation antihistamine, enhances the delayed rectifier outward K current (I) in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this study, we aimed to determine the effects of CPH on neuronal excitability in current-clamped pyramidal neurons in mouse medial prefrontal cortex slices. CPH (10 µmol/L) significantly reduced the current density required to generate action potentials (APs) and increased the instantaneous frequency evoked by a depolarizing current. CPH also depolarized the resting membrane potential (RMP), decreased the delay time to elicit an AP, and reduced the spike threshold potential. This effect of CPH was mimicked by a sigma-1 receptor agonist and eliminated by an antagonist. Application of tetraethylammonium (TEA) to block I channels hyperpolarized the RMP and reduced the instantaneous frequency of APs. TEA eliminated the effects of CPH on AP frequency and delay time, but had no effect on spike threshold or RMP. The current-voltage relationship showed that CPH increased the membrane depolarization in response to positive current pulses and hyperpolarization in response to negative current pulses, suggesting that other types of membrane ion channels might also be affected by CPH. These results suggest that CPH increases the excitability of medial prefrontal cortex neurons by regulating TEA-sensitive I channels as well as other TEA-insensitive K channels, probably I and inward-rectifier Kir channels. This effect of CPH may explain its apparent clinical efficacy as an antidepressant and antipsychotic.
Animals
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Cyproheptadine
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pharmacology
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Female
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Histamine H1 Antagonists
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pharmacology
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Membrane Potentials
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drug effects
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physiology
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Mice, Inbred C57BL
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Patch-Clamp Techniques
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Potassium Channel Blockers
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pharmacology
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Potassium Channels
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metabolism
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Prefrontal Cortex
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drug effects
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physiology
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Pyramidal Cells
;
drug effects
;
physiology
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Receptors, sigma
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agonists
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metabolism
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Tetraethylammonium
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pharmacology
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Tissue Culture Techniques