Role of transmitters in mediating hypothalamic control of electrolyte excretion.

Changes in urinary volume and electrolyte excretion were monitored after the injection of cholinergic and monoaminergic drugs into the third cerebral ventricle of conscious male rats made diuretic by an intravenous infusion of 5% dextrose. A natriuretic and kaliuretic response was induced by the intraventricular injection of norephrine (NE) or carbachol, whereas dopamine (DA) had no effect. The beta-receptor stimulator isoproterenol (ISO) induced an antinatriuretic and antikaliuretic effect. Intraventricular injection of the alpha-adrenergic blocker phentolamine abolished the natriuretic response to NE and carbachol and to intraventricular hypertonic saline (HS). By contrast, the beta-adrenergic blocker propranolol induced a natriuresis and kaliuresis when injected alone and an additive effect when its injection was followed by NE or HS. Propranolol potentiated the natriuretic response to carbachol. Cholinergic blockade with atropine diminished the response to NE and blocked the natriuretic response to HS. It is suggested that sodium receptors in the ventricular wall can modify renal sodium excretion via a stimulatory pathway involving cholinergic and alpha-adrenergic receptors and can inhibit sodium excretion via a tonically active beta-receptor pathway.     

The role of GABA in dyskinesias induced by chemical stimulation of the striatum

The gamma aminobutyric acid (GABA) antagonists picrotoxin and bicuculline were injected into the striatum of rats via chronic cannulae. Dyskinesias were produced by these drugs which could be blocked by their injection combined with GABA. The intrastriatal (i.s.) injection of a cholinergic drug, carbachol, also produced dyskinesias which were blocked by GABA. The use of i.s. injection of GABA antagonists to produce an animal model of Huntington's chorea is discussed.     

Progress toward understanding the neurophysiological basis of predator-induced morphology in Daphnia pulex

Previous studies have demonstrated that certain pesticides, including carbaryl and endosulfan, can modulate the expression of predator-induced morphology in Daphnia. These pesticides affect the transmission of nervous impulses in vertebrates and invertebrates. The aim of this study was to determine the role of two neurotransmitter systems, excitatory cholinergic transmission and inhibitory gamma-aminobutyric acid (GABA)-mediated transmission, in the regulation of inducible defenses of Daphnia. The effects of chemicals with four different modes of action on the expression of Chaoborus-induced neckteeth in Daphnia pulex were measured. These chemicals included chemicals that could enhance transmission at cholinergic synapses (physostigmine, nicotine), inhibit cholinergic transmission (atropine), stimulate or enhance the effects of GABA (diazepam, muscimol, cis-4-aminocrotonic acid), or antagonise the action of GABA (picrotoxin, bicuculline, SR95531). The development of Chaoborus-induced neckteeth in D. pulex was enhanced by physostigmine and picrotoxin and suppressed by atropine. It was proposed that these chemicals were acting on neurosecretory cells that release the hormones necessary to induce neckteeth development. The results also indicate mechanisms through which anthropogenic pollutants could influence the expression of inducible defenses, leading to inappropriate expression in environments with low predator intensity or to suppression in environments with high risks of predation.     

Changes in succinate dehydrogenase activity of rats after intraventricular injections of GABA, muscimol and picrotoxin

Effects of intraventricular injections of GABA, and a GABA agonist, muscimol and an antagonist, picrotoxin on succinate dehydrogenase (SDH) enzyme activity in plasma and a few hypothalamic nuclei of brain of rats have been investigated using biochemical, histochemical and cytophotometric techniques. Results show that SDH decreased by GABA and muscimol treatment, and increased after picrotoxin injection. From the above findings, it is apparent that GABA, muscimol and picrotoxin influence SDH activity of plasma and hypothalamic nuclei.     

Butyrylcholinesterase fluctuation in male albino rats with intracerebroventricular injection of gamma aminobutyric acid, muscimol, and picrotoxin

The effects of intracerebroventricular injection of gamma-Aminobutyric acid, muscimol, or picrotoxin have been studied on butyrylcholinesterase (BuChE) activities in the serum and several hypothalamic nuclei using biochemical, histochemical, and cytophotometric techniques, respectively. The blood samples were withdrawn from indwelling catheters in jugular vein 1, 15, 30, 45, 60, 90, and 120 min after injection of the drugs. Biochemical estimations demonstrated a significant inhibition of BuChE after GABA and muscimol injections, whereas a pronounced stimulation of BuChE was observed after injection of picrotoxin. The peak changes were observed within 30 min of drug injection. Cytophotometric studies have appeared to dovetail the biochemical findings. Only a marginal decrease was observed after injection of GABA in all nuclei, while muscimol induced a very conspicuous decrease of BuChE. On the contrary, intracerebroventricularly administered picrotoxin markedly increased the levels of BuChE activity. Thus it could be concluded that probably GABA and muscimol along with picrotoxin appear to alter BuChE.     

Evidence that GABA in the nucleus dorsalis raphé induces stimulation of locomotor activity and eating behavior

Recent electrophysiological studies have provided evidence that GABA controls inhibitorily the activity of the serotonin containing cell bodies in nucleus dorsalis raphé (NDR). The present investigation shows that local injection of baclofen or the GABA agonist muscimol (25–100 ng) into the NDR strongly increased locomotor activity and stimulated eating in satiated rats. These effects are antagonized by the GABA antagonists bicuculline or picrotoxin given systemically or locally. Muscimol injected in NDR also decreased serotonin and 5-hydroxyindole acetic acid in hypothalamus but not in striatum. These findings support a transmitter role of GABA in NDR and may be interpreted related to a decreased activity of serotonin.     

Comparative actions of GABA and acetylcholine on the Xenopus laevis lateral line

The effects of GABA, acetylcholine and carbachol on the spontaneous activity of afferent nerve fibers in the lateral line of Xenopus laevis are characterized. Atropine and bicuculline were also tested on drug- and water motion-evoked activity. GABA (0.019-1.25 mM) suppressed and both acetylcholine (1.25-80 microM) and carbachol (1.25-40 microM) increased spontaneous activity. These actions were blocked by bicuculline (100 microM) and atropine (4 microM) respectively. Atropine (20 microM) and bicuculline (100 microM) had no effect on water motion-evoked activity. The results characterize actions of GABA and acetylcholine not previously described and provide evidence that does not support the hypothesis that GABA or acetylcholine are the afferent transmitter.     

Assessment of some transmitter actions in rat cerebellar slices

The effects of 100 microM norepinephrine (NE), GABA, aspartate, glutamate, and carbachol on the release of endogenous NE, GABA, aspartate, and glutamate from slices of rat cerebellum were examined. The 35 mM K+-stimulated release of NE was potentiated by GABA (136% of control), glutamate (123%), and carbachol (123%); aspartate had no effect. Glutamate increased the release of GABA to 250% of control levels, while neither NE nor carbachol exerted any effect. Glutamate and GABA increased aspartate release to 260% and 300% of control values, respectively. NE decreased the release of aspartate to 86% of control levels while carbachol had no effect. The stimulated release of glutamate was increased by GABA (166% of control) but was unaffected by NE and carbachol. All of these effects were observed only under depolarizing conditions and in the presence of extracellular Ca2+. These data suggest a cholinergic, GABAergic and glutamatergic control of the noradrenergic system in the cerebellum; the presence of a specific aspartergic system in the cerebellum; and a net excitatory action of GABA may be present within the cerebellum.     

Involvement of chloride channel coupled GABA(C) receptors in the peripheral antinociceptive effect induced by GABA(C) receptor agonist cis-4-aminocrotonic acid

We investigated the effect of chloride and potassium channel blockers on the antinociception induced by GABA(C) receptor agonist CACA (cis-4-aminocrotonic acid) using the paw pressure test, in which pain sensitivity was increased by an intraplantar injection (2 microg) of prostaglandin E(2) (PGE(2)). CACA administered locally into the right hindpaw (25, 50 and 100 microg/paw) elicited a dose-dependent antinociceptive effect which was demonstrated to be local, since only higher doses produced an effect when injected in the contralateral paw. The GABA(C) receptor antagonist (1,2,5,6 tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA; 5, 10 and 20 microg/paw) antagonized, in a dose-dependent manner, the peripheral antinociception induced by CACA (100 microg), suggesting a specific effect. This effect was reversed by the chloride channel coupled receptor blocker picrotoxin (0.8 microg/paw). Glibenclamide (160 microg) and tolbutamide (320 microg), blockers of ATP-sensitive potassium channels, charybdotoxin (2 microg), a large-conductance potassium channel blocker, dequalinium (50 microg), a small-conductance potassium channel blocker, and cesium (500 microg), a non-specific potassium channel blocker did not modify the peripheral antinociception induced by CACA. This study provides evidence that activation of GABA(C) receptors in the periphery induces antinociception, that this effect results from the activation of chloride channel coupled GABA(C) receptors and that potassium channels appear not to be involved.     

Relationship of urinary kallikrein excretion to urinary potassium excretion during furosemide administration with and without amiloride

The relationship of urinary kallikrein excretion to urine volume, and to urinary sodium and potassium excretions was studied in normal rats during furosemide diuresis and superimposed injection of amiloride, a K+-sparing diuretic. Continuous infusion of furosemide increased urinary kallikrein, sodium and potassium excretions and the urine volume. Amiloride injection during furosemide diuresis caused further increase in diuresis and natriuresis, but a prompt decrease in urinary kallikrein excretion to basal level, and potassium excretion to below the basal level. The significant correlation of urinary kallikrein excretion to urinary potassium excretion, but not to urine volume and urinary sodium excretion after amiloride injection suggests that the major determinant of urinary kallikrein excretion is renal potassium secretion through a mechanism that is affected by amiloride.     

Qualitative and quantitative changes in monoamine oxidase activity after acute third ventricle treatment of GABA, muscimol, and picrotoxin in rat

The effect of acute IIIrd ventricle injection of GABA, muscimol, and picrotoxin on the activity of monoamine oxidase (MAO) has been investigated in serum and a few hypothalamic nuclei of the rat brain using biochemical, histochemical, and cytophotometric techniques. Biochemical estimation demonstrated a significant reduction in MAO enzyme activity after GABA and muscimol injection, whereas picrotoxin produced pronounced increase in the enzyme activity. Histochemical and cytophotometric studies confirmed the biochemical findings. Even in brain, GABA and muscimol inhibited and picrotoxin stimulated the MAO activity. From the above findings, it may be concluded that GABA, muscimol, and picrotoxin regulate the MAO activity, possible mechanisms for which are being discussed.     

Muscarinic modulation of GABAergic transmission to neurons in the rat subfornical organ

Cholinergic actions on subfornical organ (SFO) neurons in rat slice preparations were studied by using whole cell voltage- and current-clamp recordings. In the voltage-clamp recordings, carbachol and muscarine decreased the frequency of GABAergic inhibitory postsynaptic currents (IPSCs) in a dose-dependent manner, with no effect on the amplitudes or the time constants of miniature IPSCs. Meanwhile, carbachol did not influence the amplitude of the outward currents induced by GABA. Furthermore, carbachol and muscarine also elicited inward currents in a TTX-containing solution. From the current-voltage relationship, the reversal potential was estimated to be -7.1 mV. These carbachol-induced responses were antagonized by atropine. In the current-clamp recordings, carbachol depolarized the membrane with increased frequency of action potentials. These observations suggest that acetylcholine suppresses GABA release through muscarinic receptors located on the presynaptic terminals. Acetylcholine also directly affects the postsynaptic membrane through muscarinic receptors, by opening nonselective cation channels. A combination of these presynaptic and postsynaptic actions may enhance activation of SFO neurons by acetylcholine.     

安定降低家兔血压和减少刺激下丘脑诱发室性期前收缩的机制分析

家兔62只,用乌拉坦(700mg/kg)和氯醛醣(35mg/kg)静脉麻醉,三碘季铵酚制动,在人工呼吸下进行实验。用电刺激下丘脑近中线区的方法诱发室性期前收缩(HVE)。静脉注射安定(0.5mg/kg)可降低基础血压(BP),减弱刺激下丘脑引起升压反应(指收缩压峰值SBP_(max))和减少HVE。在双侧延髓腹外侧头端区(rVLM)微量注射氟安定(200μg溶于0.5μl中),γ-氨基丁酸(GABA)(6μg溶于0.5μl中)均能降低BP、SBP_(max)和减少HVE,若微量注射印防己毒素(7.5μg溶于0.5μl中)则可使BP上升并增多HVE。而于双侧延髓腹外侧尾端区(cVLM)微量注射同样剂量氟安定、GABA则无上述反应。安定降低BP、SBP_(max)和减少HVE的作用可被双侧rVLM区微量注射GABA受体拮抗剂荷包牡丹碱(3μg溶于0.5μl中)或印防己毒素所消除,但在双侧rVLM区微量注射甘氨酸受体拮抗剂士的宁(1μg溶于0.5μl中)、阿片受体拮抗剂纳洛酮(0.5μg溶于0.5μl中)、胆碱能阻断药阿托品(0.25μg溶于0.5μl中)、东莨菪碱(1.5μg溶于0.5μl中)后仍然存在。 上述结果提示,在双侧rVLM应用GABA受体拮抗剂可消除安定降低BP、SBP_(max)和减少HVE的作用,安定降低BP、SBP_(max)和减少HVE的作用可能通过GABA这一中间环节,而胆碱能受体、阿片受体、甘氨酸受体可能不起重要作用。     

家兔延髓腹外侧区内注射荷包牡丹碱对安定降低心脏功能的影响

家兔48只,用乌拉坦(1g/kg)静脉麻醉,三碘季铵酚制动,在人工呼吸下进行实验。静脉注射安定(0.5mg/kg)以及侧脑室注射氟安定(2mg溶于50μl人工脑脊液中)或γ-氨基丁酸(GABA)(300μg溶于50μl人工脑脊液中)都可降低心室内压峰值(PLVP),减少心力环面积(ACFL)和心室内压最大上升速率(dp/dt_(max))。安定和氟安定对PLVP、ACFL和dp/dt_(max)的抑制作用可被预先在侧脑室注射GABA受体拮抗剂印防己毒素(15μg溶于50μl人工脑脊液中)或双侧延髓腹外侧头端区(γVLM)微量注射GABA受体拮抗剂荷包牡丹碱(3μg溶于0.5μl生理盐水)所阻断。而在延髓网状巨细胞核中间部、网状小细胞核、孤束核或面神经核内注射同样剂量的荷包牡丹碱则不能阻断。 这些结果提示:延髓腹侧部GABA受体的激活可抑制心脏功能,安定对心脏功能的抑制作用可能通过激活延髓腹侧区GABA受体而实现。     

Renal response to secretin.

The effect of Jorpes secretin on the urinary volume, pH, and excretion of sodium, potassium, chloride, bicarbonate, titratable acidity, ammonia and phosphate was studied in five healthy male volunteers with and without simultaneous aspiration of duodenal fluids. A three- to fourfold increase in urinary volume and sodium excretion occurred within the first 30 min after secretin injection and this was accompanied by a significant rise in urinary pH in each instance. Urinary bicarbonate excretion increased from 55 plus or minus 13 to 395 plus or minus 33 mueq/30 min after secretin injection. Aspiration of alkaline duodenal contents was accompanied by an even greater postsecretin increase in urinary bicarbonate excretion. No significant changes in arterial pH or blood gases were detected throughout the study. These observations are compatible with a direct effect of secretin upon the renal tubular reabsorption of water, bicarbonate, and other ions, and could account for the transient alterations in urinary pH occurring in response to a meal.     

Centrally administered GABA and GABA-selective agonist and antagonist in rats: histoenzymological cytophotometric study

In the present study, the effect of intracerebroventricular (icv) injection of GABA, its agonist--muscimol, and antagonist--picrotoxin, has been studied on histoenzymological alterations of acetylcholinesterase (AChE). butyrylcholinesterase (BuChE), monoamine oxidase (MAO), and succinic dehydrogenase (SDH) by cytophotometric technique. This study was conducted on medial preoptic area (mPOA), nucleus paraventricularis hypothalami (PVH), area lateralis hypothalami (LHA), nucleus dorsomedialis hypothalami (DMH), and nucleus ventromedialis hypothalami (VMH). Results showed that GABA and muscimol inhibited AChE, BuChE, MAO, and SDH in all the areas while picrotoxin stimulated these enzymes. These changes in enzyme activity by GABA, muscimol, and picrotoxin and their possible mode of action are discussed.     

Cholinergic transmission via central synapses in the locust nervous system

In this study we examine the nature of chemical synaptic transmission between identified filiform hair receptors on the prothoracic segment of a locust and the identified postsynaptic projection interneuron (A4I1). The effects of pressure ejected acetylcholine, and various ligands of acetylcholine receptors on the activity of the postsynaptic neuron A4I1, or on wind-elicited responses in A4I1 are reported. It is suggested that the transmitter of the afferent fibers is acetylcholine, and that fast transmission is mediated by nicotinic acetylcholine-receptors. Both nicotine and carbachol act as agonists, whereas d-tubocurarine and alpha-bungarotoxin act as antagonists. The presence of muscarinic acetylcholine receptors was also evident from the modulatory effects of muscarine, oxotremorine and pilocarpine, which were blocked by bath application of atropine. GABA, and its agonists muscimol and cis-4-amino-crotonic-acid lead to inhibition of A4I1 responses. This inhibition was prevented by the additional application of picrotoxin. This suggests involvement of a ligand-gated GABA receptor which, most likely, increases chloride conductance. Metabotropic GABA-receptors do not seem to be involved, since baclofene, diazepam and bicuculline ejections had no effects. Glutamate also inhibits wind elicited A4I1 responses. Although attempts were made to further characterize the receptor involved, tested substances such as kainic acid, glycine, CNQX or GDEE had no effect.     

Stress-Induced Enhancement of Suppression of [3H]GABA Release from Striatal Slices by Presynaptic Autoreceptor

The effect of cold and immobilization stress on presynaptic GABAergic autoreceptors was examined using the release of [3H]GABA (gamma-aminobutyric acid) from slices of rat striatum. It was found that in vitro addition of delta-aminolevulinic acid, as well as GABA agonists such as muscimol and imidazoleacetic acid, exhibited a significant suppression of the striatal release of [3H]GABA evoked by the addition of high potassium, whereas delta-aminovaleric acid had no significant effects on the evoked release. These suppressive actions were antagonized invariably by the GABA antagonists, bicuculline and picrotoxin, but not by the glycine antagonist, strychnine. Cholinergic agonists, such as pilocarpine and tetramethylammonium, also attenuated significantly the evoked release of [3H]GABA from striatal slices, while none of its antagonists, including atropine, hexamethonium and d-tubocurarine, affected the release. On the other hand, in vitro addition of dopamine receptor agents such as dopamine, apomorphine, and haloperidol, or the inhibitory amino acids, glycine, beta-alanine, and taurine failed to influence the evoked release of [3H]GABA from striatal slices. Application of a cold and immobilization stress for 3 h was found to induce a significant enhancement of the suppressive effects by muscimol and delta-aminolevulinic acid on the evoked release of [3H]GABA, without affecting that by pilocarpine and tetramethylammonium. These results suggest that the release of GABA from striatal GABA neurons may be regulated by presynaptic autoreceptors for this neuroactive amino acid, and may play a significant functional role in the exhibition of various symptoms induced by stress.     

The effects of TRH on prolactin, plasma renin activity, water and electrolyte excretion in normal males.

The effect of TRH induced secretion of TSH and prolactin (hPrl) on plasma renin activity (PRA), water and electrolyte excretion, was studied in 7 normal males before and after an intravenous injection of 2 ml normal saline or 200 microgram TRH. Plasma hPrl and TSH rose significantly (p less than 0.01) in all 7 subjects after TRH but not after saline injection. No significant differences in the hourly excretion of sodium, potassium and free water clearance were noted before and after either saline or TRH injection. Mean PRA values of the 7 subjects were similar after either the 2 ml saline of TRH injection. Our results indicate that despite a correlation between basal hPrl and sodium excretion as well as free water clearance, acute TRH induced elevation of hPrl is not associated with changes of urinary sodium and potassium excretion, free water clearance and PRA in normal males. These findings provide some evidence against a direct osmoregulatory role of hPrl in man.     

A Search for Receptors Modulating the Release of γ-[3H]Aminobutyric Acid in Rabbit Caudate Nucleus Slices

Various putative striatal transmitters and related compounds were studied for their effects on the release of gamma-aminobutyric acid (GABA) from slices of the head of the rabbit caudate nucleus. The slices were preincubated with [3H]GABA and then superfused and stimulated electrically at 5 or 20 Hz. Aminooxyacetic acid was present throughout. The main changes observed were the following. The basal and, less consistently, the electrically evoked overflow of [3H]GABA were enhanced by 3,4-dihydroxyphenylethylamine (dopamine), an effect not blocked by cis-flupentixol or domperidone and not mimicked by apomorphine and D1-selective agonists. The electrically evoked overflow was diminished by 5-hydroxytryptamine (serotonin); the inhibition was prevented by methiothepin. The basal but not the electrically evoked overflow was enhanced by carbachol; acetylcholine and nicotine also accelerated the basal outflow whereas oxotremorine caused no consistent change; the effect of carbachol and acetylcholine were blocked by hexamethonium but not by atropine or by tetrodotoxin. These findings indicate that the GABA neurons in the caudate nucleus may be stimulated by dopamine, although the receptor type involved remains unclear; inhibited by serotonin; and stimulated by acetylcholine acting via a nicotine receptor. However, all drug effects observed were relatively small. No evidence was obtained for autoreceptors, alpha 2-adrenoceptors or receptors for opioids, adenosine or substance P at the GABA neurons.