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Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Earlier investigations of sympathomimetic drugs overcoming the amnesic action of cycloheximide (CXM) in day-old chickens were extended to biochemical studies in vitro. The effects of amphetamine, norepinephrine, alpha and beta noradrenergic stimulants and receptor blockers on Na+/K+ ATP'ase activity in total homogenate of chicken forebrain were investigated. Norepinephrine and the beta stimulant, isoprenaline significantly stimulated the activity of this enzyme, while the beta blocker, propranolol inhibited activity. Amphetamine, the alpha stimulant, methoxamine and the alpha receptor blocker, piperoxane had no effect on Na/K+ ATP'ase activity in total homogenate. In a purified synaptosomal preparation, both amphetamine (5 X 10(-5) M) and norepinephrine (1 X 10(-4) M) produced a slight stimulation of Na+/K+ ATP'ase activity. A similar concentration of amphetamine (1.12 X 10(-4) M) did not inhibit 14C-leucine uptake or incorporation into protein in the synaptosomal fraction. Nor was it able to alleviate CXM inhibition of 14C-leucine incorporation into synaptosomal protein. The results are interpreted in terms of amphetamine (via release of norepinephrine) norepinephrine and isoprenaline stimulating and maintaining the labile, sodium pump-dependent, phase of memory formation for a sufficient length of time until protein synthesis inhibition by CXM wears off.
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PMID:Biochemical actions of sympathomimetic drugs which overcome cycloheximide-induced amnesia. 13 58

Non-nucleated red blood cells from rats contain adenyl cyclase, the activity of which is predominantly localized in the reticulocytes. Basal enzyme activities in membrane preparations from reticulocyte-rich blood (pretreatment of rats with acetyl-phenylhydrazide: about 60% reticuloytes) are about 5 times higher than in preparations from reticulocyte-poor blood (untreated animals: 2-3% reticulocytes). The enzyme activities are stimulated 10-fold by sodium fluoride (10(-2)M) and 6 to 8-fold by isoprenaline (10(-4)M). Adenyl cyclase activities in membrane preparations from reticulocyte-rich and reticulocyte-poor blood can be ascribed to identical enzymes since identical apparent Km (ATP; 3 times 10(-4)M, Ka (isoprenaline; 3 times 10(-6)M) and Ki (propranolol vs. isoprenaline; 3 times 10(-7)M) values were obtained in both preparations. Besides NaF, only phenylethanolamine derivatives with beta-adrenergic receptor stimulant properties were effective as stimulators of adenyl cyclase activity. The affinities (apparent Ka values) of the investigated compounds decreased in the order isoprenaline--hexoprenaline--fenoterol--salbutamol--adrenaline--terbutalin--noradrenaline--phenylephrine. For maximal intrinsic activity, the catechol structure was essential; the relative intrinsic activities of resorcinol derivatives did not exceed 0.6. The isoprenaline-stimulated adenyl cyclase activities in erythrocyte membrane preparations were competitively inhibited by beta-adrenergic blocking drugs, the affinities (apparent Ki values) decreasing in the order prindolol--penbutolol--propranolol--practolol. The dextrorotatory enantiomers of penbutolol and propranolol were 1/100 to 1/200 as active as the resp. levorotatory enantiomers. From experiments with alpha-adrenergic agonists (e.g. phenylephrine) and antagonists (e.g. phentolamine), it is concluded that alpha-adrenergic receptors do not interfere with the beta-adrenergically-mediated cAMP formation in these particular membranes. A variety of hormones and drugs known to stimulate denyl cyclase activities in various tissues, e. g. ACTH, glucagon, STH, erythropoietin, prostaglandin E1 etc. did not affect adenyl cyclase activity in reticulocyte-rich erythrocyte membrane preparations. In contrast to adenyl cyclase activity, phosphodiesterase activities in erythrocyte membrane and cytoplasmic fractions were only twice as high in reticulocyte-rich as in reticulocyte-poor preparations. From the experiments described, it is obvious that the adenyl cyclase of the rat reticulocyte is subject to monovalent-hormonal, i.e. beta-sympathomimetic stimulation. Moreover, the premature red blood cell provides a useful model for quantitative studies of the interaction of drugs with the beta-adrenergic receptor.
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PMID:The beta-adrenergic receptor-adenyl-cyclase system of rat reticulocytes: effects of adrenergic stimulants and inhibitors. 24 Jan 35

The polypeptide apamin caused a small depolarization of the muscle cell membrane of the guinea-pig taenia coli accompanied by enhancement of spike activity and a concomitant muscle contration. The membrane hyperpolarization evoked by intramural stimulation of the non-adrenergic inhibitory nerves (inhibitory junction potential) was reduced by apamin; the antagonism being non-competitive in nature. The rebound depolarization and contraction following the inhibitory junction potential was enhanced by apamin. The membrane hyperpolarization induced by the purinergic compound ATP and by the sympathomimetic adrenaline was converted to a depolarization in the presence of apamin. This depolarization resulted in an increased spike activity and muscle contraction. This was followed by membrane hyperpolarization and muscle relaxation after washout of the drugs. These findings indicate that apamin is a non-competitive, non-specific antagonist of the non-adrenergic inhibitory transmitter and that the inhibitory junction potential and the rebound are mutually independent phenomena.
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PMID:The effect of apamin on the smooth muscle cells of the guinea-pig taenia coli. 49 45

Amnesia resulting from inhibition of cerebral protein synthesis by cycloheximide can be prevented by subcutaneous injection of the monoamine oxidase inhibitor pargyline (25 mg/kg) or the sympathomimetic amine metaraminol (3.0 mg/kg) administered up to 30 min following learning of a single trial passive avoidance task in day-old chickens. The injection has to be made during the life time of labile memory for the prevention of cycloheximide-induced amnesia. On the other hand, amnesia induced by the Na/K ATP'ase inhibitor ouabain can only be prevented if these two agents are administered up to 5 min after learning, i.e. during the life time of short-term memory. In addition, both agents produce a retrieval deficit 90 min after the injection, but only when memory is in long-term storage. These results are compared to those obtained with administration of norepinephrine, d-amphetamine and diphenylhydantoin.
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PMID:Similar effects of a monoamine oxidase inhibitor and a sympathomimetic amine on memory formation. 50 14

A sympathetic neurone blocking drug, guanethidine, and a tachykinin antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (rpwwL-SP), partially inhibited the contractile response to nicotine to the same degree in the isolated detrusor strips of guinea-pig urinary bladder. Application of rpwwL-SP completely abolished the inhibitory effect of guanethidine on the nicotine-induced contraction, suggesting that the tachykinin(s)-ergic transmission might be involved in the sympathomimetic effect of nicotine. Conversely, when the preparation was treated with guanethidine to block release of a mediator from the sympathetic nerve, the inhibitory effect of rpwwL-SP was diminished, suggesting an exclusive contribution of the sympathetic nerve communications to the action of the tachykinin(s). We previously suggested that nicotine may release acetylcholine and ATP to contract the detrusor strips, and that acetylcholine output may be increased by an unknown substance released from the sympathetic nerve by nicotine. In preparations treated with atropine, rpwwl-SP had no effect on the nicotine-induced contraction. The concentration-response curves for carbachol and ATP were not influenced by rpwwl-SP. After tachyphylaxis to capsaicin developed, the nicotine-induced contraction was not affected. It is suggested that in guinea-pig detrusor, tachykinin(s) from capsaicin-insensitive sites is (are) involved in the excitatory sympathomimetic effect of nicotine, and that the tachykinin(s) behave(s) as a modulator finally to increase the acetylcholine output from the parasympathetic cholinergic nerve.
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PMID:Mechanism of action of nicotine in isolated urinary bladder of guinea-pig: involvement of tachykinin(s) released by nicotine in the drug's sympathomimetic effect. 248 45

In isolated perfused rat liver, addition of adrenaline induced a complex response of bile flow including rapid, reversible stimulation (1/2-2 min), reversible inhibition (2-10 min), and prolonged stimulation. Both the reversible stimulation and the inhibition were mimicked by the alpha-sympathomimetic agonist phenylephrine but not by the beta-agonist isoproterenol. The reversible stimulation was a very early effect being terminated prior to all other alpha-adrenergic responses of liver. External ATP considerably lowered bile flow while inducing release of glucose and lactate, inhibition of respiration, and a reversible efflux of Ca2+. Variations of mannitol clearance parallel to those of bile flow indicate a canalicular origin of all changes.
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PMID:Regulation of canalicular bile formation by alpha-adrenergic action and by external ATP in the isolated perfused rat liver. 299 44

1. Nicotine produced a transient contraction of isolated strips of guinea-pig urinary bladder. The response to nicotine was antagonized by the nicotinic receptor antagonist, hexamethonium but was insensitive to tetrodotoxin. 2. The nicotine-induced contraction was potentiated by the cholinesterase inhibitor, physostigmine, and was reduced to 50% and 70% by the muscarinic cholinoceptor antagonist, atropine and the sympathetic neurone blocking drug, guanethidine, respectively. Chemical denervation with 6-hydroxydopamine abolished the inhibitory effect of guanethidine. Simultaneous treatment with atropine and guanethidine did not abolish the response to nicotine, but the degree of inhibition was comparable to that obtained with atropine alone. 3. The nicotine-induced contraction was insensitive to bunazosin and yohimbine (alpha 1- and alpha 2-adrenoceptor antagonists, respectively), and exogenously applied noradrenaline did not cause a contraction even in the presence of blockade of noradrenaline uptake mechanisms with desipramine and normetanephrine and of beta-adrenoceptors with propranolol, suggesting a non-adrenergic nature of the sympathomimetic effect of nicotine in this tissue. 4. The nicotine-induced contraction in the presence of atropine was abolished after desensitization of P2-purinoceptors with alpha, beta-methylene adenosine 5'-triphosphate, a slowly degradable ATP analogue selective for P2-purinoceptors. By this desensitization, the response to ATP, but not to histamine, was also abolished. 5. A cyclo-oxygenase inhibitor flurbiprofen partially inhibited the nicotine-induced contraction. The degree of the inhibition was more pronounced in the presence of atropine than in its absence. Flurbiprofen antagonized the response to exogenously applied ATP in an unsurmountable manner, but not that to carbachol. 6. The present results suggest that nicotine might induce a contraction through an interaction with nicotinic receptors located on the terminals of, possibly, (i) parasympathetic cholinergic, (ii) sympathetic non-adrenergic and (iii) non-sympathetic purinergic nerves in guinea-pig detrusor preparations, and that a portion of the contraction due to the purine nucleotide released is possibly potentiated by intramural prostaglandin(s). Parasympathetic cholinergic output might be modulated by an unknown excitatory substance released by nicotine from sympathetic nerve. 7. Nicotine reveals a latent excitatory effect of the sympathetic hypogastric nerve which innervates guinea-pig detrusor.
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PMID:Mechanism of action of nicotine in isolated urinary bladder of guinea-pig. 322 73

Isoprenaline, a sympathomimetic drug used in the treatment of asthma, was found to be sulphated by the bronchial tissues of the monkey and dog. Enzyme preparations of the liver, small intestine and kidney of various animals are also able to catalyze this sulphate conjugation reaction from ATP and inorganic sulphate and from a commercial preparation of adenosine 3'-phosphate 5'-sulphatophosphate (PAP35S) or PAP35S generated from Na235SO4 in vitro. The Km values for isoprenaline for the sulphotransferase of mouse liver and monkey lung, are respectively, 51,3 microM and 138 microM . The significance of this detoxication reaction is discussed in relation to (a) the importance of lung as a potential biotransformation site of isoprenaline, (b) asthma deaths supposed to be associated with the use of isoprenaline in the form of pressurised aerosols and (c) the ability of the different tissues to synthesize PAPS in vitro.
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PMID:Sulphate conjugation of isoprenaline by lung, small intestine and other organs. 705 52

The effects of the transmembrane pH gradient (delta pH) and the transmembrane potential gradient (delta psi) on the uptake of several sympathomimetic amines were investigated, using bovine adrenal chromaffin granules isolated in isotonic sucrose. As previously described [R. Johnson and A. Scarpa, J. Biol. Chem. 254 3750 (1979)], freshly isolated chromaffin granules maintain an intragranular pH of 5.5 as measured by [14C] methylamine distribution and, in the presence of ATP, generate a delta psi of 80 mV, positive inside, as measured by [14C] methylamine distribution. When tyramine, metaraminol, and isoproterenol (1-50 mM) were added to well-buffered suspensions of granules at pH 7.0, a dose-related alkalinization of the granule interior was observed. Study of the time-resolved influx of the same amines labeled radiochemically (5-21 microM) revealed that all the amines were accumulated against an apparent concentration gradient. However, while accumulation of [14C] serotonin and [3H] isoproterenol was totally inhibited by reserpine, [14C] tryramine accumulation was inhibited by only 60% and [14C[ metaraminol uptake was unaffected. The ATP-dependent generation of a delta psi produced a stimulation of amine uptake in the order: serotonin greater than isoproterenol greater than tyramine; metaraminol accumulation was not enhanced by ATP addition. The relationship between the electrochemical proton gradient (delta micro H+) and the electrochemical gradient for each of the sympathomimetic amines (delta micro A) was investigated utilizing chromaffin ghosts devoid of endogenous matrix gradients or components. All amines were accumulated in the presence of delta pH alone. In the presence of delta psi alone, [14C] serotonin, (14C] tyramine, and [3H] isoproterenol were accumulated, but no [3H] metaraminol uptake was demonstrable. The results indicate that serotonin and isoproterenol accumulated in isolated chromaffin granules and ghosts via a reserpine-sensitive mechanism, driven by the magnitude of the electrochemical proton gradient. Conversely, metaraminol permeated the membrane of the chromaffin granule through the apolar lipid phase and distributed according to the delta pH alone. Tyramine uptake proceeded by both mechanisms. The implications of the mechanism of accumulation of these potent physiologic and pharmacologic agents for their in vivo action are discussed.
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PMID:Mechanisms of accumulation of tyramine, metaraminol, and isoproterenol in isolated chromaffin granules and ghosts. 708 50

Contractions, release of noradrenaline and release of ATP elicited by the indirectly acting sympathomimetic amine tyramine and responses elicited by exogenous noradrenaline were studied in the isolated vas deferens of the guinea pig. Release of noradrenaline was assessed as overflow of tritium after preincubation with [3H]-noradrenaline. ATP was measured by means of the luciferin-luciferase technique. In tissues pretreated with pargyline 1 mM, tyramine 300 microM, when added to the superfusion medium for 2 min, elicited contraction and an overflow of tritium (mainly [3H]-noradrenaline) and ATP. Contraction and ATP overflow responses were prevented and tritium overflow was greatly reduced by desipramine 10 microM. Prazosin 0.3 microM abolished contractions and evoked ATP overflow without changing tritium overflow. Blockade of postjunctional P2-purinoceptors by suramin 300 microM caused a marked decrease of tyramine-evoked contractions and a slight reduction of tritium overflow whereas evoked ATP overflow was markedly increased. The effect on contraction was not shared by two other P2-purinoceptor antagonists, namely pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) 32 microM and diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) 32 microM: PPADS increased contractions about fourfold, whilst DIDS had no effect at all. When the vas deferens was superfused for 24 min with medium containing tyramine 300 microM, evoked contractions and tritium overflow continued throughout whereas ATP overflow faded rapidly to basal values. In the presence of prazosin 0.3 microM, tyramine 300 microM again failed to elicit contractions as well as an overflow of ATP. Application of noradrenaline 10 microM instead of tyramine also resulted in prolonged contraction and an overflow of ATP that declined rapidly. It is concluded that all ATP released by tyramine is non-neuronal in origin, secondary to the activation of postjunctional alpha 1-adrenoceptors by released noradrenaline. The non-neural ATP does not seem to play a functional role in smooth muscle contraction and derives from a postjunctional source which is subject to a rapid depletion upon sustained alpha 1-adrenoceptor activation.
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PMID:Failure of tyramine to release neuronal ATP as a cotransmitter of noradrenaline in the guinea-pig vas deferens. 871 58


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