Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Intracellular recordings were made from submucosal neurones of the guinea-pig ileum. The actions of noradrenaline, somatostatin and [Met5]enkephalin on nicotinic synaptic potentials (EPSPs) were studied. 2. In one series of experiments, agonists were applied by superfusion; noradrenaline (0.1-20 microM) decreased EPSP amplitude by 95-100% in all neurones. Similar application of somatostatin (1-100 nM) inhibited EPSPs in about half the neurones by a maximum of 40%. [Met5]enkephalin (0.1-10 microM) did not alter EPSPs. Idazoxan and yohimbine competitively antagonized the action of noradrenaline with dissociation equilibrium constants of 20 and 30 nM respectively. 3. In another series of experiments, noradrenaline and somatostatin were applied locally from a pipette so that they reached presynaptic terminals but not the cell bodies or axons of the presynaptic cell: noradrenaline inhibited EPSPs by 90% in all neurones but somatostatin had no effect. When applied locally to the cell bodies giving rise to the presynaptic fibres, both agonists inhibited EPSPs in half the neurones by 40%. 4. When noradrenaline was applied locally to presynaptic terminals, the latency to onset of noradrenaline to inhibit EPSPs was 45-160 ms; cadmium applied similarly depressed EPSPs in 5-50 ms. 5. Pertussis toxin pre-treatment only partially blocked presynaptic inhibition caused by noradrenaline but abolished the reduction of EPSP amplitude by somatostatin. 6. It is concluded that noradrenaline and somatostatin reduce the amplitude of the fast EPSP because they hyperpolarize cell bodies and prevent action potential initiation. Noradrenaline, but not somatostatin, has an additional action to inhibit acetylcholine release by acting at nerve terminal receptors. 7. The presynaptic inhibitory action of noradrenaline results from activation of alpha 2-adrenoceptors at nerve terminals but the mechanism(s) by which these presynaptic receptors act cannot be explained adequately by either activation of a potassium conductance and/or inhibition of a calcium conductance.
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PMID:Mechanisms underlying presynaptic inhibition through alpha 2-adrenoceptors in guinea-pig submucosal neurones. 198 22

1. The effect of exogenous dopamine on the release of endogenous acetylcholine (ACh) from isolated ileal synaptosomal guinea-pig preparations was examined by means of high pressure liquid chromatography with electrochemical detection. 2. Release of ACh was induced by substance P or by depolarization with high potassium (50 mM) in a medium containing atropine propranolol and naloxone. 3. Dopamine produced a concentration-dependent inhibition of the evoked ACh release induced by substance P or in samples depolarized by high potassium. This action of dopamine was not reversed by the dopamine receptor antagonists either for the DA2 subtype domperidone, or for the DA1 subtype, SCH23390. Fenoldopam, the agonist of dopamine DA1 receptors, or quinpirole, the agonist of dopamine DA2 receptors, reduced the evoked ACh release, although only in high, non-dopamine-specific concentrations. 4. Failure of guanethidine or desipramine to inhibit this effect of dopamine ruled out mediation by endogenous noradrenaline. 5. Idazoxan and yohimbine reversed this dopamine-induced inhibition at concentration sufficient to abolish the action of clonidine. Influx of (45)Ca stimulated by substance P or high potassium into synaptosomal preparations was attenuated in the presence of dopamine. This inhibition by dopamine was also reversed by idazoxan or yohimbine but not by dopamine receptor antagonists. Moreover, the dopamine-induced inhibitions of both the ACh release and the influx of (45)Ca disappeared in the samples treated with pertussis toxin at a dose sufficient to abolish the action of clonidine. 6. It is concluded that dopamine suppresses the influx of calcium ions into cholinergic nerve terminals via an activation of alpha2-adrenoceptors coupled with a pertussis toxin-sensitive GTP-binding protein, resulting in the decrease of ACh release from ileal synaptosomes of guinea-pigs.
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PMID:Dopamine-induced inhibition of endogenous acetylcholine release from the isolated ileal synaptosomal preparations of guinea-pig mediated via alpha-adrenoceptors. 752 17

Arginine contains the guanidinium group and thus has structural similarity to ligands of imidazoline and alpha-2 adrenoceptors (alpha-2 AR). Therefore, we investigated the possibility that exogenous arginine may act as a ligand for these receptors in human umbilical vein endothelial cells and activate intracellular nitric oxide (NO) synthesis. Idazoxan, a mixed antagonist of imidazoline and alpha-2 adrenoceptors, partly inhibited L-arginine-initiated NO formation as measured by a Griess reaction. Rauwolscine, a highly specific antagonist of alpha-2 AR, at very low concentrations completely inhibited NO formation. Like L-arginine, agmatine (decarboxylated arginine) also activated NO synthesis, however, at much lower concentrations. We found that dexmedetomidine, a specific agonist of alpha-2 AR was very potent in activating cellular NO, thus indicating a possible role for alpha-2 AR in L-arginine-mediated NO synthesis. D-arginine also activated NO production and could be inhibited by imidazoline and alpha-2 AR antagonists, thus indicating nonsubstrate actions of arginine. Pertussis toxin, an inhibitor of G proteins, attenuated L-arginine-mediated NO synthesis, thus indicating mediation via G proteins. L-type Ca(2+) channel blocker nifedipine and phospholipase C inhibitor U73122 inhibited NO formation and thus implicated participation of a second messenger pathway. Finally, in isolated rat gracilis vessels, rauwolscine completely inhibited the L-arginine-initiated vessel relaxation. Taken together, these data provide evidence for binding of arginine to membrane receptor(s), leading to the activation of endothelial NO synthase (eNOS) NO production through a second messenger pathway. These findings provide a previously unrecognized mechanistic explanation for the beneficial effects of L-arginine in the cardiovascular system and thus provide new potential avenues for therapeutic development.
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PMID:Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells. 1753 4