PARTICIPATION OF AN UNUSUAL GANGLIONIC PATHWAY IN THE MEDIATION OF THE PRESSOR EFFECT OF PHYSOSTIGMINE IN THE RAT.
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In spinal rats physostigmine failed to produce a pressor response even after treatment of the animals with hexamethonium, whereas noradrenaline, McN-A-343 (4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride) and AHR602 (3-acetoxy-1-benzyl-1-methylpyrrolidinium bromide) all produced large pressor effects. In rats anaesthetized with urethane, hexamethonium completely abolished the pressor effect of dimethylphenylpiperazinium but only partially blocked the pressor response to physostigmine; pressor effects of noradrenaline, McN-A-343 and AHR602 were potentiated. Combined treatment with hexamethonium and atropine and with hexamethonium and cocaine, however, completely abolished the pressor effect of physostigmine; simultaneously the pressor effects of McN-A-343 and AHR602 as well as of dimethylphenylpiperazinium were also blocked. P-286 (N-diethylaminoethyl-N-isopentyl-N'N'-di-isopropylurea) produced an early and a late block of the pressor effect of physostigmine; the initial block was due to an adrenergic blocking action while the late block was probably due to a dual action of the drug in abolishing the effects of both the nicotinic and non-nicotinic ganglion stimulants. Pressor responses to physostigmine, McN-A-343, AHR602 and dimethylphenylpiperazinium were abolished immediately after ganglion-blocking doses of nicotine. It is suggested that an unusual ganglionic pathway participates in the mediation of the pressor response to physostigmine in the rat, especially when the established ganglionic pathways are blocked. (+info)
INNERVATION OF THE LARGE INTESTINE OF THE TOAD (BUFO MARINUS).
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The morphology, physiology and pharmacology of the innervation of the toad (Bufo marinus) large intestine have been studied. The large intestine can be divided into the regions colon, rectum and cloaca, on morphological grounds, but acts as a unit in response to nerve stimulation. Of the right and left nerves, each appears to supply the entire large intestine. Autonomic innervation of the large intestine of Bufo marinus is as follows: (1) The 9th and 10th spinal nerves (pelvic) contain predominantly excitatory preganglionic cholinergic fibres, but some inhibitory adrenergic fibres are also present in most preparations. (2) The splanchnic nerves contain inhibitory postganglionic adrenergic fibres from the 3rd to 5th sympathetic ganglia, and a small number of excitatory cholinergic fibres. The pathway of adrenergic inhibitory fibres to the large intestine alongside the posterior mesenteric artery as seen in mammals is rarely present in the toad. Several nonspecific actions of autonomic drugs on the large intestine are discussed. The functional organization of the autonomic innervation of the toad large intestine is similar to that in mammals, that is the large intestine is controlled by antagonistic cholinergic and adrenergic nerves. However, the separation of these two types of nerve fibres into anatomically distinct nerves does not appear to be as complete as in mammals. It is suggested that inhibitory autonomic control of the alimentary canal in vertebrates first appears in the hind-gut region. (+info)
A PRELIMINARY INVESTIGATION OF THE PHARMACOLOGY OF THE HUMAN ISOLATED TAENIA COLI PREPARATION.
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The effects of drugs on smooth muscle strips of human taenia coli, obtained from operation specimens, were studied in vitro. Both nicotinic and muscarinic sites of action of acetylcholine were demonstrated, the nicotinic effect being a relaxation. The sympathomimetic amines, adrenaline, noradrenaline, and isoprenaline produced a relaxation of the tissue by an action on adrenaline alpha- and beta-receptors. The presence of both types of receptor was demonstrated by selective adrenergic blockade with pronethalol or Hydergine. Pronethalol in high concentrations gave a nonselective adrenergic blockade. The ganglion-stimulating agents nicotine and dimethylphenylpiperazinium produced a relaxation of the tissue in all concentrations. This relaxation was inhibited by pronethalol or physostigmine but no contractile component to ganglion stimulation was revealed when these two drugs were present together. These results indicate the presence of either sympathetic ganglia in the intrinsic nerve plexuses, or adrenergic stores in the bowel wall. There is no pharmacological evidence for parasympathetic ganglia in human sigmoid colon. Histamine produced relaxant, contractile or biphasic responses. The type of response was independent of the "tone" of the preparation. The responses were not modified by procaine, hyoscine or pronethalol, which result indicates that both the contractile and relaxant responses to histamine were due to a direct action of the drug on smooth muscle. 5-Hydroxytryptamine produced either a contraction or a relaxation of the tissue. The relaxation was due to a direct effect of the drug, since hexamethonium, procaine or pronethalol did not affect the response. No conclusions have been drawn regarding the mechanism of the contractile response to 5-hydroxytryptamine. The nature of the responses of the tissue to drugs was independent of the disease for which the specimen of colon was removed. (+info)
THE EFFECTS OF PHYSOSTIGMINE ON THE MECHANICAL AND ELECTRICAL RESPONSES OF THE CAT NICTATING MEMBRANE.
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The effects of physostigmine on the electrical and mechanical responses of the nictitating membrane elicited by single nerve shocks have been studied in cats anaesthetized with a mixture of chloralose and pentobarbitone. The results were variable but the most consistent effect, observed with large doses of physostigmine, was a depression and prolongation of the contractions which was sometimes associated with augmentation of the characteristic rhythmic electrical activity of the smooth muscle. Although the amplitude of single responses was depressed, incomplete tetanic contractions were sometimes increased in tension because of the greater fusion which occurred as a result of prolongation of the units of contraction. Possible mechanisms underlying the effect of physostigmine are discussed. (+info)
THE MECHANISM OF THE PRESSOR RESPONSES TO PHYSOSTIGMINE IN THE RAT AND THEIR MODIFICATION BY MEBUTAMATE AND AMYLOBARBITONE.
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Pressor responses to intravenous injections both of physostigmine and of pilocarpine were smaller in rats anaesthetized with either mebutamate or amylobarbitone than in rats anaesthetized with urethane. The response to electrical stimulation of the hypogastric nerve in the isolated hypogastric nerve-vas deferens preparation was diminished by mebutamate and by amylobarbitone, but not by urethane. Similar results were obtained with the cat isolated splenic nerve-spleen preparation. In the rat anaesthetized with urethane, pressor responses to physostigmine were only partially antagonized by hexamethonium but were completely abolished during "depolarizing" ganglionic block by nicotine or tetramethylammonium. It is suggested that, in addition to the central mechanism, there is a peripheral component in the pressor action of physostigmine and in the antihypertensive actions of mebutamate and amylobarbitone. (+info)
Antagonism of sevoflurane anaesthesia by physostigmine: effects on the auditory steady-state response and bispectral index.
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BACKGROUND: Physostigmine, a centrally acting anticholinesterase, antagonizes the hypnotic effect of propofol, as shown by the return of consciousness (response to commands) or wakefulness (spontaneous eye-opening without response to commands) and by recovery of auditory evoked potentials (40 Hz auditory steady-state response (ASSR)) and the bispectral index (BIS). We measured the effects of physostigmine on the hypnotic effect of inhaled volatile anaesthetics, using sevoflurane as the representative agent. METHODS: Eight healthy volunteers received sevoflurane adjusted to produce loss of consciousness. Physostigmine (plus glycopyrrolate) was given while the end-tidal concentration of sevoflurane was kept constant. RESULTS: Loss of consciousness was accompanied by a significant (P<0.02) decrease in ASSR amplitude (to 21% of awake value) and BIS (to 70% of awake value). Five subjects had return of consciousness or wakefulness after physostigmine. The others showed no behavioural change. Physostigmine caused a significant increase of the mean ASSR amplitude from 0.11 (SD 0.04) to 0.17 (0.06) microV (P<0.05). The BIS also increased, from 66 (12) to 74 (12), but the difference was not significant. CONCLUSIONS: Physostigmine can antagonize, at least partially, the hypnotic effect of sevoflurane and changes in arousal after physostigmine are shown by ASSR measurements. However, the antagonism is not as clear or reliable as with propofol. (+info)
Dual sensory-motor function for a molluskan statocyst network.
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In mollusks, statocyst receptor cells (SRCs) interact with each other forming a neural network; their activity is determined by both the animal's orientation in the gravitational field and multimodal inputs. These two facts suggest that the function of the statocysts is not limited to sensing the animal's orientation. We studied the role of the statocysts in the organization of search motion during hunting behavior in the marine mollusk, Clione limacina. When hunting, Clione swims along a complex trajectory including numerous twists and turns confined within a definite space. Search-like behavior could be evoked pharmacologically by physostigmine; application of physostigmine to the isolated CNS produced "fictive search behavior" monitored by recordings from wing and tail nerves. Both in behavioral and in vitro experiments, we found that the statocysts are necessary for search behavior. The motor program typical of searching could not be produced after removing the statocysts. Simultaneous recordings from single SRCs and motor nerves showed that there was a correlation between the SRCs activity and search episodes. This correlation occurred even though the preparation was fixed and, therefore the sensory stimulus was constant. The excitation of individual SRCs could in some cases precede the beginning of search episodes. A biologically based model showed that, theoretically, the hunting search motor program could be generated by the statocyst receptor network due to its intrinsic dynamics. The results presented support for the idea that the statocysts are actively involved in the production of the motor program underlying search movements during hunting behavior. (+info)
A pharmacological study of the spontaneous convulsive activity induced by 1,2-dihydroxybenzene (catechol) in the anaesthetized mouse.
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1. The convulsive activity induced by catechol has been examined in anaesthetized mice either by determining the CD50 for the convulsions in drug-treated and control animals, or by studying the effects of various drugs on the total whole body activity. 2. The results indicate that catecholamines play no part in the mechanism of action of catechol. Drugs which alter cerebral catecholamine levels had no effect on the convulsions, nor did the alpha- and beta-adrenoceptor blocking drugs. 3. 5-Hydroxytryptamine (5-HT) could possibly be important, though results with drugs which either change brain 5-HT levels, or block 5-HT receptors were inconsistent. 4. gamma-Aminobutyric acid also appears not to be involved in the mechanism of action of catechol. 5. The results strongly suggest that catechol primarily activates a central cholinergic system, in that muscarinic and nicotinic receptor blocking drugs inhibit, and anticholinesterases potentiate the convulsions. (+info)