Responses of septal nuclei neurons to microiontophoretically administered putative neurotransmitters

In halothane anesthetized rats, neurons of the medial and lateral septal nuclei were tested with iontophoretically applied putative neurotransmitters. GABA, norepinephrine, serotonin, and acelycholine in roughly this order of potency were inhibitory with respect to spontaneous and evoked activity of both medial and lateral septal nuclei cells. No specific effects of any of the compounds were observed on septal unit responses to fornix or fimbria stimulation.     

A presynaptic component of the action of iontophoretically applied flurazepam on feline cortical neurones.

The effect of iontophoretically applied flurazepam on the spike activity of pericruciate cortical neurones of the cat was studied. Flurazepam increased cortical inhibition produced either by local electrical stimulation (which is known to release gamma-aminobutyric acid (GABA) or by iontophoretically applied GABA. Following intravenous treatment with thiosemicarbazide (a GABA-synthesis inhibitor), flurazepam still augmented the action of GABA but was much less effective on electrically evoked cortical inhibition. These findings suggest that part of the action of flurazepam on inhibitory cortical transmission might be at the presynaptic level.     

Sensitivities of Achatina giant neurones to putative amino acid neurotransmitters

1. GABA receptors in Achatina identifiable giant neurones were classified into the muscimol I, muscimol II and baclofen types. Muscimol I and II type GABA receptors were sensitive to GABA and muscimol but insensitive to baclofen, whereas baclofen type receptors were sensitive to GABA and baclofen but insensitive to muscimol. Muscimol I and baclofen types were associated with the inhibition caused by GABA, while muscimol II type with the GABA excitation.2. GABA, muscimol and TACA produced a transient outward current (I_out) with an increase in membrane conductance (g) of an Achatina neurone, TAN, having the muscimol I type GABA receptors. Their relative potency values (RPV) at GABA ed₅₀ (approximately 10⁻⁴ M) were: GABA: muscimol: TACA = 1:0.6:0.3. The GABA effects were potentiated by pentobarbitone, antagonized competitively by pitrazepin and non-competitively by picrotoxin and diazepam, and unaffected by bicuculline. The ionic mechanism of effects of GABA and its two analogues was the increase in membrane Cl⁻ conductance (g_Cl).3. GABA and (±)-baclofen produced a slow I_out with a g increase of another Achatina neurone, RPeNLN, having the baclofen type GABA receptors. The two compounds were almost equipotent (ed₅₀: approximately 3 × 10⁻⁴ M). The ionic mechanism of their effects was the increase in g_k. The two compounds hardly affected the voltage-gated and slowly inactivating calcium current. I_out produced by GABA and (±)-baclofen were reduced by TEA, but unaffected by 4-AP, bicuculline, pitrazepin and picrotoxin.4. β-hydroxy-l-glutamic acid (l-BHGA) showed the marked effects on the Achatina giant neurones; the two neurones were excited by the compound, whereas the three inhibited. D-BHGA, l-Glu, d-Glu and NMDA were less effective than l-BHGA or almost ineffective. Erythro-l-BHGA was more or less effective than threo-l-BHGA according to the neurones tested.5. α-Kainic acid and domoic acid excited the two neurones, which were excited by l-BHGA. l-Quisqualic acid showed the similar effects to l-BHGA, which were mostly much stronger than l-BHGA. Erythro-l-tricholomic acid and dl-ibotenic acid showed the effects similar to l-BHGA selectively on some neurones.6. It was pointed out that the pharmacological features of GABA on the Achatina neurones are simpler than those of l-BHGA, due to the simpler structure of the former compound having less binding sites than the latter.     

Effect of curare on responses to different putative neurotransmitters in Aplysia neurons.

We have studied the effects of curare on responses resulting from iontophoretic application of several putative neurotransmitters onto Aplysia neurons. These neurons have specific receptors for acetylcholine (ACh), dopamine, octopamine, phenylethanolamine, histamine, gamma-aminobutyric acid (GABA), aspartic acid, and glutamic acid. Each of these substances may on different specific neurons elicit at least three types of response, caused by a fast depolarizing Na+, a fast hyperpolarizing Cl-, or a slow hyperpolarizing K+ conductance increase. All responses resulting from either Na+ or Cl- conductance increases, irrespective of which putative transmitter activated the response, were sensitive to curare. Most were totally blocked by less than or equal to 10-4 M curare. GABA responses were less sensitive and were often only depressed by 10-3 M curare. K+ conductance responses, irrespective of the transmitter, were not curare sensitive. These results are consistent with a model of receptor organization in which one neurotransmitter receptor may be associated with any of at least three ionophores, mediating conductance increase responses to Na+, Cl-, and K+, respectively. In Aplysia nervous tissue, curare appears not to be a specific antagonist for the nicotinic ACh receptor, but rather to be a specific blocking agent for a class of receptor-activated Na+ and Cl- responses.     

Effect of curare on responses to different putative neurotransmitters in Aplysia neurons

We have studied the effects of curare on responses resulting from iontophoretic application of several putative neurotransmitters onto Aplysia neurons. These neurons have specific receptors for acetylcholine (ACh), dopamine, octopamine, phenylethanolamine, histamine, γ-aminobutyric acid (GABA), aspartic acid, and glutamic acid. Each of these substances may on different specific neurons elicit at least three types of response, caused by a fast depolarizing Na⁺, a fast hyperpolarizing Cl^?, or a slow hyperpolarizing K⁺ conductance increase. All responses resulting from either Na⁺ or Cl^? conductance increases, irrespective of which putative transmitter activated the response, were sensitive to curare. Most were totally blocked by ≤ 10^?4 M curare. GABA responses were less sensitive and were often only depressed by 10^?3 M curare. K⁺ conductance responses, irrespective of the transmitter, were not curare sensitive. These results are consistent with a model of receptor organization in which one neurotransmitter receptor may be associated with any of at least three ionophores, mediating conductance increase responses to Na⁺, Cl^?, and K⁺, respectively. In Aplysia nervous tissue, curare appears not to be a specific antagonist for the nicotinic ACh receptor, but rather to be a specific blocking agent for a class of receptor-activated Na⁺ and Cl^? responses.     

Effects of putative neurotransmitters on the motor activity of Spirometra mansonoides.

5-Hydroxytryptamine (5-HT), epinephrine, and dopamine strongly stimulated the motor activity of larval Spirometra mansonoides. By contrast, a cholinomimetic agent, arecoline, paralyzed the worms. There was some pharmacological specificity among the agonists but not with various antagonists. Acetylcholinesterase activity was present in both larval and adult Spirometra.     

Interaction between morphine and putative excitatory neurotransmitters in cortical neurons in naive and tolerant rats.

Microelectrophoretically applied morphine depressed spontaneously discharging cortical neurones of rats and blocked excitation induced by electrophoretic administrations of either acetylcholine or l-glutamate. This depressant effect and both the anti-acetylcholine and the anti-glutamate effect were naloxone antagonizable and therefore regarded as specific morphine actions. The excitatory effects of morphine were not affected by naloxone application and were classified as non-specific.In chronically morphinized rats the depressant effect of morphine on spontaneous discharge activity and also its blocking action upon acetylcholine and l-glutamate-induced excitation were almost completely abolished. The predominant response in such pre-treated animals was non-specific excitation. Acetylcholine and l-glutamate were found to be more effective in tolerant rats (supersensitivity).     

The role of calcium in monoamine-induced depression of cerebral cortical neurones

The calcium antagonists, lanthanum, verapamil and manganese, have been shown to antagonize the depressant actions of ionto-phoretically applied monoamines (noradrenaline, 5-hydroxytryptamine, dopamine and histamine), but not of γ-aminobutyric acid, on cerebral cortical neurones. Cocaine and ethanol, which also affect membrane calcium fluxes, have a similar antagonistic action. These findings suggest that calcium ions are essential for, and perhaps mediate, the characteristic depressant actions of the monoamines on cerebral cortical neurones.     

Neomycin and ruthenium red antagonism of monoaminergic depression of cerebral cortical neurones

Neomycin and ruthenium red, two agents which are known to interfere with the transport and binding of calcium, antagonize the depressant actions of noradrenaline and 5-hydroxytryptamine on cerebral cortical neurones. Ouabain and sodium azide, metabolic inhibitors, also block the action of noradrenaline. These findings support earlier suggestions that monoaminergic depression of cortical neurones involves a calcium-dependent mechanism which may be linked to a membrane ion pump.     

The actions of some putative neurotransmitters on the cockroach salivary gland.

1. Certain putative transmitters were applied to the innervated cockroach salivary gland and their effects on the resting potential and the neurally evoked secretory potential of the acinar cells were observed. 2. gamma-Aminobutyric acid, glutamate, glycine, aspartate and alanine had no significant effect on the resting potential. However, gamma-aminobutyric acid and glutamate reduced the neurally evoked secretory potential but only at concentrations above 10(-3) M3. Acetylcholine and carbachol appeared to act by modifying transmitter output from the salivary nerves. These substances failed to have any effect on the resting potential. 4. The biogenic amines, adrenaline, dopamine, noradrenaline, 5-hydroxy-tryptamine and octopamine, produced hyperpolarizing responses, graded according to concentration. 5. It is suggested that dopamine, the most potent of the biogenic amines tested, is the transmitter at this junction.     

Sensitivity of Aplysia neurons in primary culture to putative neurotransmitters

Aplysia neurons grown in primary cell culture (Dagan and Levitan, 1981) were exposed to the putative neurotransmitters acetylcholine and serotonin by local iontophoretic application, and changes in membrane potential or voltage clamp currents were examined. It was found that 47% of the neurons were sensitive to cholinergic agonists, 14% to serotonin, and 9% responded to both. Responses could be recorded upon application of the transmitters to the cell bodies as well as along the regenerated neurites. An identified group of neurons, the neurosecretory bag cells, exhibited similar responses to cholinergic agonists in culture and in situ. Pleural medial neurons exhibited cholinergic responses in culture similar to those previously reported in situ. Thus neurotransmitter receptor/ion channel complexes characteristic for a specific cell type in the intact ganglion are also present on this cell type in culture.     

A first mathematical approximation of cerebral cortical responses to cerebello-thalamic signals using a thermodynamic analogue.

A mathematical approximation is developed to predict cerebral cortical responses CTX(t, x, R) at a distance R (R greater than or equal to 0) from a focal point in the cerebral cortex, at a depth x (0 less than or equal to x less than or equal to 500 mu) from the cortical surface and at any time t, to thalamic signals THAL(t) whose amplitudes also vary with time t. The equation is derived from a thermodynamic analogue, which is the time dependent heating of a focus at the surface of a semi-infinite solid.     

Effects of some putative amino acid neurotransmitters on the stimulated TSH secretion in male rats

The importance of several amino acids (glycine, L-glutamic acid, L-serine, taurine and beta-alanine) in the regulation of the stimulated secretion of TSH was studied in male rats using both peripheral and central administration of the amino acids. Glycine (10-200 mg/kg i.p.), L-glutamic acid (10-500 mg/kg i.p.) and L-serine (500 mg/kg i.p.) decreased significantly the cold-induced TSH secretion whereas beta-alanine (1-500 mg/kg i.p.) and taurine (10-100 mg/kg i.p.) were not effective. The effect of L-glutamic acid (100 mg i.p.) was partially antagonized by bicuculline (1 mg/kg i.p.) but not by picrotoxin (1 or 2 mg/kg i.p.). Only glycine (50 and 100 mg/kg i.p.) inhibited the TRH-stimulated TSH secretion. When the intracerebroventricular route was used, L-serine (50 micrograms/rat) decreased the TSH could response whereas glycine and L-glutamic acid (1-50 micrograms/rat) had no clear effect. We conclude that glycine, glutamate and serine inhibit the cold-induced TSH secretion in the male rat. The action of serine and glycine is possibly mediated through the periventricular hypothalamus and the anterior pituitary, respectively. The inhibition caused by glutamate seems to be partially mediated through the bicuculline-sensitive GABA receptors in the hypothalamus. Taurine and beta-alanine play no role in the control of rat TSH secretion.     

Effects of adenosine analogs on rat cerebral cortical neurons

Adenosine and the adenosine 5'-phosphates (5'-AMP, 5'-ADP and 5'-ATP) depress the spontaneous firing of cerebral cortical neurons. In this study adenosine analogs, adenosine transport blockers and adenosine deaminase inhibitors have been used to gain further insight into the nature of the adenosine receptor and the likely routes of metabolism of extracellularly released adenosine. The firing rate of cortical neurons, including identified corticospinal neurons, was depressed by 2-substituted derivatives of adenosine. 2-Halogenated derivatives of adenosine were potent depressors while 2-aminoadenosine and 2-hydroxyadenosine (crotonoside) were slightly less potent than adenosine. The α,β-methylene isosteres of 5'-ADP and 5'-ATP were almost devoid of agonist activity while the β,γ-methylene analog was an active agonist. This suggests that ADP and ATP must be converted to AMP or possibly adenosine before they can activate the adenosine receptor. 2'-, 3'- and 5'- deoxyadenosine depressed spontaneous firing without antagonizing the effect of adenosine. Adenosine deaminase inhibitors, deoxycoformycin and $\text{erythro}$-9-(2-hydroxy-3-nonyl) adenine had potent, long lasting depressant actions on the spontaneous firing of cortical neurons and concurrently potentiated the actions of adenosine or 5'-AMP. Inhibitors of adenosine transport, papaverine and 2-hydroxy-5-nitrobenzylthioguanosine, prolonged the duration of action of adenosine and 5'-AMP. Intracellular recordings show that 5'-AMP hyperpolarizes cerebral cortical neurons and suppresses spontaneous and evoked excitatory postsynaptic potentials, in the absense of any pronounced alterations in membrane resistance.     

Antagonism of biogenic amine-induced depression of cerebral cortical neurones by Na+, K+-ATPase in inhibitors.

The effects of iontophoretically applied Na+-, K+-dependent adenosinetriphosphatase (Na+,K+-ATPase) (EC 3.6.1.3) inhibitors (ouabain, digitoxin, digitoxigenin, strophanthin K, strophanthidin, thevetin A and B, ethacrynate, and harmaline) on the depression of rat cerebral cortical neurones by noradrenaline, 5-hydroxytryptamine, and histamine have been studied. The inhibitors antagonized depressions of spontaneously active neurones evoked by these amines, but not those evoked by gamma-aminobutyric acid, adenosine, adenosine 5'-monophosphate, or calcium. The antagonistic potencies of the various inhibitors appeared to be proportional to their known potencies as inhibitors of Na+, K+-ATPase. The data therefore support the hypothesis that amines depress central neurones by activating an electrogenic sodium pump.