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At least 73 records · Page 4Linked to original sources
PubMed1983

Lack of stereoselectivity in ability of nicotine to release dopamine from rat synaptosomal preparations.

Both the naturally occurring (-)-isomer and the synthetic (+)-isomer of nicotine caused release of 3H from a crude synaptosomal fraction of rat brain preincubated with [3H]dopamine. The isomers were equipotent in producing this response, which was concentration-dependent, a significant effect on the fractional release of dopamine being observed at 10(-4) M nicotine. The effect did not appear to be the result of synaptosomal damage, as levels of the intrasynaptosomal marker lactate dehydrogenase did not increase in the supernatant. Nicotine-induced release was inhibited by removal of external Ca2+ and by the presence in vitro of pempidine (230 microM). Neither hexamethonium (500 microM) in vitro nor the chronic administration of (-)-nicotine in vivo had any effect on the nicotine-induced release of [3H]dopamine. It is concluded that nicotine exerts this effect via a presynaptic nicotinic receptor of the "ganglionic" type, but that this receptor differs from that in the periphery by showing a relative lack of stereospecificity. There is no evidence of a functional "down regulation" in this receptor on chronic exposure to nicotine in vivo.

Animals↗
PubMed1969

Investigation of the spasmogenic effect of manganese on the guineapig isolated ileum preparation.

1. The mechanism of the manganese-induced spasm of the guinea-pig ileum was investigated using agents known to modify nerve function. The spasm was reduced by cooling, tetrodotoxin, procaine, Botulinus toxin (Type A), hyoscine and pempidine. It was potentiated by mipafox.2. In the presence of manganese, the release of acetylcholine from the ileum was greatly increased.3. Tetrodotoxin prevented the manganese-induced increase in acetylcholine output from the ileum but had no significant effect on the spontaneous acetylcholine output.4. It is suggested that the manganese-induced spasm of the ileum results from an action on intramural cholinergic nerves.

Acetylcholine↗
PubMed1973

The detection of differential beta-adrenoceptor blockade in the cat.

1. Tachycardia and bronchodilatation were produced by intravenous dimethylphenylpiperazinium iodide (DMPP) in the spinal or pithed cat. Responses other than those involving beta-adrenoceptors were minimized by appropriate blocking agents.2. With intact adrenals, both the tachycardia and bronchodilatation with 10 mug/kg DMPP were equal to those with 1 mug/kg adrenaline.3. After adrenalectomy, tachycardia with 100 mug/kg DMPP was equal to that with 1.5 mug/kg adrenaline, but the bronchodilatation was equal to that with only 0.3 mug/kg. This difference may reflect the relative activity of the sympathetic supply to the organs.4. After adrenalectomy, propranolol was 3 times as effective against bronchodilatation due to DMPP as against tachycardia. Practolol was inactive against bronchodilatation.5. With intact adrenals, propranolol reduced both tachycardia and bronchodilatation due to DMPP equally. Propranolol also antagonized equally both effects of adrenaline in the pithed cat after adrenalectomy.6. In the spinal cat, propranolol caused bradycardia and bronchoconstriction that persisted after adrenalectomy or pithing. It was reduced by pempidine and guanethidine and is attributed to spontaneous adrenergic neuronal activity.7. The Appendix describes a device for cycle-by-cycle spirometry and correction for zero drift of a micromanometer, used in this study for the continuous recording of bronchial resistance.

Adrenalectomy↗
PubMed1974

The specificity of some agonists and antagonists for nicotine-sensitive receptors in ganglia.

1 The guinea-pig isolated ileum has been used to estimate the ability of substituted phenylalkylonium salts (related to nicotine) to stimulate or block receptors in ganglia. The effects of hexamethonium were used to indicate which were the most specific ganglion stimulants; these were tested on the blood-pressure of pithed rats and for neuromuscular blocking activity on the rat diaphragm preparation.2m-Hydroxyphenylpropyltrimethylammonium and 3,4-dihydroxyphenethyltrimethylammonium (coryneine, ;quaternary dopamine') were the most active and specific ganglion stimulants but their usefulness in vivo may be limited by their neuromuscular blocking activity. The analogous tertiary compounds are being investigated.3 The affinities of substances which were blocking agents at ganglionic receptors were measured on the isolated ileum with m-hydroxyphenylpropyltrimethylammonium as agonist. The affinities of selected compounds for postganglionic receptors were measured in experiments on the ileum in the presence of hexamethonium and with carbachol as agonist. Some of the compounds were tested for neuromuscular blocking activity on the rat diaphragm.4 Phenylbutyldiethylamine had ganglion-blocking activity greater than pempidine and little postganglionic blocking or neuromuscular blocking activity. Its triethylammonium analogue had higher ganglion-blocking activity but had appreciable neuromuscular blocking activity.5 The aromatic ring system is not essential either for activity or affinity and the effects of substituents are not related to their effects on electron distribution. Stimulant activity is enhanced only by hydroxyl or amino groups in suitable positions; it is not improved by the presence of rigid features (double or triple bonds or a cyclopropane ring) in the side chain. Affinity is slightly increased by chloro or bromo groups in suitable positions but the unsubstituted compounds are among those with the highest affinity. Substituents have similar effects on affinity for postganglionic receptors, though for these receptors the compounds mostly have only about one-tenth of their affinity for ganglionic receptors.

Animals↗
PubMed1974

Effects of nicotine given into the brain of fowls.

1 The effects of nicotine, given into the IIIrd ventricle of adult conscious fowls (Gallus domesticus) or infused into various brain regions of conscious young chicks, were tested on behaviour, electrocortical activity, respiratory rate and body temperature. Its effects given intraventricularly or applied externally to the brain-stem of anaesthetized fowls were also examined.2 After intraventricular nicotine, fowls squatted for 3 to 5 min with eyes closed, electrocortical activity resembling that during sleep but with superimposed spike activity. Following this, fowls reawakened and tachypnoea developed, together with partial abduction of the wings from the trunk, the back becoming horizontal and the tail flexed. These effects were prevented by pempidine.3 Intraventricular nicotine suppressed or, less commonly, reduced operant key-pecking, an effect unrelated linearly to dose.4 Intraventricular nicotine given to fowls anaesthetized with chloralose produced brief apnoea, followed by increased amplitude of respiratory excursion for about 5 minutes. Respiratory rate accelerated slightly but tachypnoea did not develop. Nicotine applied directly to the ventral brain-stem increased respiratory amplitude in three out of seven fowls.5 In anaesthetized fowls, intraventricular nicotine raised blood pressure for 2 to 3 min, an effect prolonged up to 70 min by acute bilateral vagotomy, whereas pressor effects of intravenous nicotine were extended merely two to three fold. Dividing the spinal cord at C2 prevented pressor effects of intraventricular nicotine; those of intravenous nicotine were unaltered.6 In young chicks, nicotine infused into the diencephalon, telencephalon and myelencephalon induced effects similar to those observed immediately after intraventricular nicotine, i.e. chicks squatted with closed eyes but recovered within 3 to 5 minutes. Simultaneously, electrocortical activity changed from an alert to the sleep pattern, usually with superimposed ;spike' activity. Tachypnoea and associated postural changes did not develop. Pempidine prevented the behavioural and electrocortical effects of nicotine.

Aging↗
PubMed1975

Thermoregulatory changes induced by cholinomimetic substances introduced into the cerebral ventricles of sheep.

1 Thermoregulatory responses have been recorded from Welsh Mountain sheep exposed to warm, neutral or cold environments while injections of cholinomimetic drugs and/or their antagonists have been given into a lateral cerebral ventricle. 2. Carbachol and physostigmine inhibited panting of animals at high ambient temperature (ta), caused vasoconstriction and initiated shivering at neutral ta, and accentuated shivering at low ta. Rectal temperature (tre) invariably increased. Oxotremorine had apparently identical effects. 3. Nicotine and another ganglionic stimulant, the quaternary methyl derivative of dopamine, had no effects on thermoregulation. 4. Atropine given 10 min before injections of carbachol, physostigmine or oxotremorine completely inhibited their hyperthermic effects, but pretreatment with the ganglion-blocking drug, pempidine, caused no inhibition. The cholinergic synapses that respond to cholinomimetic drugs injected into the lateral cerebral ventricles of sheep are therefore muscarinic and not nicotinic. 5. When atropine was given to sheep exposed to cold, no detectable reduction of shivering occurred and tre decreased only slightly, even with doses of atropine far greater than needed to inhibit shivering induced by physostigmine. This may be because shivering is controlled by neural pathways unaffected by drugs administered intracerebroventricularly or because the cholinergic synapses activated by physostigmine do not carry the input from cold sensors.

Animals↗
PubMed1975

Mechanical responses of rat isolated uterine horns to transmural stimulation.

1 Transmural stimulation of rat isolated uterine horns at low pulse width produced contractions. These were antagonized by hyoscine or tetrodotoxin and potentiated by physostigmine. 2 In the presence of hyoscine, and during bradykinin-induced contractions, transmural stimulation produced inhibition. This inhibition was antagonized by guanethidine, propranolol or tetrodotoxin. 3 Hexamethonium or pempidine did not affect responses to transmural stimulation. 4 It is suggested that transmural stimulation is a method of exciting cholinergic motor and noradrenergic inhibitory postganglionic neurones to the rat myometrium.

Animals↗
PubMed1991

Ultrastructural changes of crop-sac and lactotrophs after systemic or intraventricular administration of drugs enhancing cholinergic transmission in pigeons.

The ultrastructural effects of drugs enhancing, by different mechanisms, cholinergic transmission in the crop-sac (the target for prolactin secretion in birds) and the anterior pituitary lactotrophs, were studied in pigeons (Columba livia). The systemic or intraventricular administration of physostigmine, carbachol and muscarine produced maximal crop-sac stimulation with milk-like secretion, as demonstrated by the observation of ultrastructural changes in the lactiferous areas through scanning and transmission electron microscopy of the crop-sac mucosa. A marked activation was also observed in anterior pituitary lactotrophs. Crop-sac and anterior pituitary lactotrophs stimulatory effects were prevented by an atropine pretreatment, but not by mecamylamine and pempidine pretreatments. The present results suggest that muscarinic receptors at the hypothalamic and/or anterior pituitary level are involved in avian species in the control of prolactin secretion.

Animals↗
PubMed1977

[Effect of cyclic nucleotides and isopropylnoradrenaline on oxygen tension and absorption].

Isopropylnoradrenaline (ISO), 3',5'-AMP and dibutyryl-3',5'-AMP decreased the oxygen tension (pO2) in the liver and the spleen and increased the body oxygen consumption (VO2). Time dynamics of these two effects was closely correlated for ISO and 3',5'-AMP. An increase of heat output was not accompanied by any significant changes in the respiration coefficient. Pempidine and dihydroergotamine failed to prevent 3',5'-AMP effects; inderal somewhat decreased these effects. Apparently, the catecholamine influence upon pO2 was a result of the VO2 increase through 3'5'-AMP effects are largely direct, but they include the in vivo and beta-receptor component; 2',3'-AMP decreased pO2 and VO2.

Animals↗
PubMedDate not supplied

Effect of stimulation or inhibition of muscarinic or nicotinic receptors on the content of biogenic amines in various parts of rat brain.

For studying the interactions of the cholinergic and noradrenergic systems in the central nervous system rats were given muscarine or nicotine and the peripheral receptors were blocked with atropine or pempidine. After killing the animals the level of biogenic amines was determined in various parts of the brain. Evident changes were found in the levels of biogenic amines after stimulation or blockade of muscarinic or nicotinic receptors.

Animals↗
PubMed1996

[Effects of drugs on re-excitability of synapses of isolated frog ganglia].

Effects of different pharmacons on the non-excitable period (NEP) and on the relative excitable period (REP) was studied in the sympathetic ganglionic synapses of the frog (Rana esculenta). Using paired stimulation we demonstrated that hexamethonium, magnesium, pempidine, tetraethylammonium (TEA) and d-tubocurarine chlorides significantly prolonged both NEP and REP at ganglion blocking threshold concentrations. Their maximum effect occurred within 30-60 min after the start of the exposition. Hemicholine and neostigmine prolonged only NEP but not REP while lidocaine influenced neither period applying continuous repeated stimulation at low frequencies (0.1-12.5 Hz). TEA showed no effect, however, at higher frequencies (14.3-20.0 Hz) it exerted a frequency-dependent depressant effect on the amplitude of the compound action potential.

Action Potentials↗
PubMed1989

Effects of nicotinic agonists and antagonists on N-methyl-D-aspartate-induced 3H-norepinephrine release and 3H-(1-[1-(2-thienyl)cyclohexyl]-piperidine) binding in rat hippocampus.

The nicotinic agonists dimethylphenylpiperazinium iodide (DMPP) and carbachol (CARB) as well as (-)nicotine [-)NIC) were tested alone and in combination with N-methyl-D-aspartate (NMDA) for their abilities to enhance the efflux of 3H-norepinephrine (NE) from slices of rat hippocampus. CARB and (-)NIC produced small, transient increases in NE efflux, while DMPP produced larger, longlasting increases. Inasmuch as the nicotinic antagonists mecamylamine (MECA) and hexamethonium (C6) did not consistently inhibit the increases in NE efflux produced by these agonists, the role of a nicotinic receptor in mediating these responses is uncertain. CARB and DMPP enhanced the ability of NMDA to stimulate NE release, while (-)NIC did not. MECA, but not C6, was found to selectively antagonize NMDA-stimulated NE release that did not appear to involve a nicotinic receptor. Binding studies indicated that MECA and the related nicotinic antagonist pempidine produced an inhibition of NMDA-stimulated NE release by an action at the PCP receptor that is known to be linked to the NMDA receptor-ionophore complex. These data suggest that the actions of these ganglionic blocking agents on excitatory responses in the hippocampus involve inhibition of excitatory amino acid as well as nicotinic receptors.

Animals↗
PubMed1983

Appearance of enkephalin-immunoreactivity in rat adrenal medulla following treatment with nicotinic antagonists or reserpine.

Various neuroendocrine factors known to be important in the regulation of adrenal catecholamine biosynthesis were investigated for possible effects on enkephalin-like immunoreactivity (Enk-IR) in the adrenal medulla of the rat. In normal rats, the adrenal chromaffin cells were not stained for either methionine (met-) or leucine (leu-) Enk-IR. Staining for Enk-IR appeared in many chromaffin cells following denervation of the adrenal or treatment of rats with the nicotinic receptor antagonists chlorisondamine or pempidine. These observations suggest that splanchnic nerve activity normally depresses the levels of enkephalin-like peptides in chromaffin cells through a trans-synaptic mechanism involving acetylcholine release and nicotinic receptor stimulation. Paradoxically, treatment with reserpine also increased Enk-IR in chromaffin cells. However, this increase did not appear to result from the well known effect of reserpine to increase presynaptic nerve firing and tyrosine hydroxylase (TOH) activity, since no increase in Enk-IR was observed following treatment with phenoxybenzamine or 6-hydroxydopamine, drugs which also increase TOH activity through trans-synaptic mechanisms. The reserpine effect also did not appear to be mediated by a stress-induced increase in glucocorticoid hormones since glucocorticoid therapy alone did not increase adrenal Enk-IR. It is suggested that the increase in adrenal Enk-IR following reserpine may result from a direct action of reserpine on chromaffin cells.

Adrenal Medulla↗
PubMed1981

Characterization of the receptor mediating the nicotine discriminative stimulus.

The discriminative stimulus (cue) property of nicotine was studied in a T-maze paradigm, and the results were analyzed by a new statistical method. For rats trained on 0.4 mg/kg, the ED50 was 0.11 mg/kg. The enantinomer of natural nicotine (+)nicotine was much less potent, and both position isomers of nicotine were inactive. Anabasine, which is active at nicotinic cholinergic receptors, provided the nicotine cue. Cytisine, a potent nicotinic agonist in vitro, was ineffective after SC administration and this was shown to be due to its inability to enter the brain in adequate amounts. High doses of cytisine by the intracerebroventricular route partially provided the cue. The cue was blocked by low doses of mecamylamine and pempidine and by high doses of hexamethonium. The data indicate that the cue receptor is pharmacologically similar to the nicotinic cholinergic receptor in autonomic ganglia.

Alkaloids↗
PubMed1994

Stimulation by nicotine of the spontaneous release of [3H]gamma-aminobutyric acid in the substantia nigra and in the globus pallidus of the rat.

The effect of (-)-nicotine on the spontaneous release of [3H]gamma-aminobutyric acid ([3H]GABA) was studied in vitro in rat substantia nigra (SN) and globus pallidus (GP) slices. In both structures, nicotine (10(-4) M) elicited a transient increase of [3H]GABA release lasting no more than 2.5 min. At the peak of the effect, a 18.5% and 25% increase of [3H]GABA was observed in GP and SN slices, respectively. At lower concentration (10(-5) M), nicotine produced a small but significant transient increase (+8%) in GP slices whereas this concentration was ineffective in SN slices. Pempidine (10(-5) M) totally antagonized the 10(-4) M nicotine-induced effect in SN and GP. The increase of [3H]GABA release elicited by 10(-4) M nicotine was abolished when Ca2+ concentration in the superfusion medium was lowered from 2.4 to 0.4 mM. To investigate a possible dopaminergic (DA) link in the response, we examined the sensitivity of the nicotine-induced effect to DA D1 (SCH23390) and D2 (sulpiride) receptor antagonists. In SN, SCH23390 (10(-6) M) abolished the 10(-4) M nicotine-induced effect. In GP, sulpiride (10(-5) M) failed to modify the response. Moreover, SCH23390 partially reversed the nicotine-induced effect (-37%) in GP. Taken together these results indicate that nicotine differentially modulate the [3H]GABA release in SN and GP. In SN, the nicotine-induced [3H]GABA release appears to be mediated by DA neurons. In GP, only a part of the nicotinic response involved a DA link. A possible direct stimulation of nicotinic receptors localized on striato-pallidal terminals is discussed.

Animals↗
PubMed1994

NMDA and carbachol but not AMPA affect differently the release of [3H]GABA in striosome- and matrix-enriched areas of the rat striatum.

The effects of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA; 10(-3) M), N-methyl-D-aspartate (10(-3) M, in the absence of magnesium or presence of AMPA) and carbachol (10(-3) M) on the release of preloaded [3H]gamma-aminobutyric acid ([3H]GABA) from microdiscs of tissue punched out from sagittal brain slices in striosome- or matrix-enriched areas of the rat striatum have been compared. Although AMPA stimulated similarly the release of [3H]GABA in both striatal compartments, the release of [3H]GABA evoked by either N-methyl-D-aspartate (in the presence of AMPA) or carbachol was more pronounced in matrix- than in striosome-enriched areas. AMPA- and N-methyl-D-aspartate- (in the absence of magnesium) evoked responses were reduced but not abolished in the presence of tetrodotoxin (10(-6) M) in both compartments while the carbachol-evoked release of [3H]GABA was decreased by tetrodotoxin only in the matrix. The interruption of cholinergic transmission by the combined application of atropine (10(-5) M) and pempidine (10(-4) M) was without effect on the AMPA-evoked release of [3H]GABA, but it reduced the N-methyl-D-aspartate- (in the absence of magnesium or presence of AMPA) evoked release of [3H]GABA in both compartments, these reductions being of similar amplitude than those observed with tetrodotoxin.

Animals↗
PubMed1981

Inhibitory effects of GABA, L-glutamic acid and nicotine on the potassium-evoked release of substance P in substantia nigra slices of the rat.

Rat substantia nigra slices were superfused with a physiological medium containing a diluted substance P (SP) antiserum, bacitracin and serum albumin to measure SP released in superfusates. As shown by measuring the degradation of a SP-labelled derivative incubated with cerebellar slices, this medium prevented the enzymatic inactivation of SP. Potassium (K+, 50 mM) and veratridine (5 X 10(-5) M) stimulated SP release and these effects were respectively prevented in absence of calcium and in presence of tetrodotoxin (5 X 10(-7) M). GABA (5 X 10(-5) M), nicotine (10(-6) M) and L-glutamic acid (5 X 10(-5) M) reduced the K+ (50 mM)-evoked release of SP. In contrast, glycine (5 X 10(-5) M), oxotremorine (5 X 10(-5) M), D-glutamic acid (5 X 10(-5) M) and serotonin (5 X 10(-5) M) were without effect. Pempidine (10(-5) M) prevented the inhibitory effect of nicotine (10(-6) M) on the K+-evoked release of SP. Glutamic acid diethyl ester (10(-4) M) completely abolished the L-glutamic acid-induced inhibition of the K+-evoked release of SP. Picrotoxin (5 X 10(-5) M) did not influence the L-glutamic acid inhibitory effect excluding the intervention of GABAergic mechanisms.

Animals↗
PubMed1985

Evidence for purinergic transmission in mouse bladder and for modulation of responses to electrical stimulation by 5-hydroxytryptamine.

Electrical stimulation (ES) contracted superfused mouse bladder, and 10(-7) M tetrodotoxin (TTX) abolished the twitches without impairing responses to acetylcholine (ACh) or beta,gamma-methylene ATP. ES acted largely through nerves which were not cholinergic, adrenergic or histaminergic. They may be purinergic because the bladder was contracted by stable analogues of ATP, and after desensitisation by a high concentration of alpha,beta-methylene ATP the response to ES was selectively reduced. 5-Hydroxytryptamine (5-HT) at 0.03-3 X 10(-6) M and tetraethylammonium (TEA) at 0.1-10 X 10(-3) M potentiated responses to ES, on average by 64% and 182%. Pempidine had no effect on responses to ES. The action of TEA was different from that of 5-HT; potentiation of responses was greater than could be produced by 5-HT, and whereas 5-HT did not increase responses to ACh, TEA markedly increased twitch tensions. The mode of action of 5-HT is not clear.

Adenosine Triphosphate↗