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)

To test the hypothesis that domperidone stimulates gastric muscle contraction by antagonizing the inhibitory effects of dopamine on postsynaptic cholinergic neurons in the myenteric plexus, the effects of dopamine on circular muscle from the body of the guinea pig stomach were examined. Dopamine inhibited circular muscle contraction evoked by electric field stimulation in a dose-related manner. The threshold dose was 10(-6) mol/L and half-maximal inhibition occurred at 10(-5) mol/L. Preincubation of muscle contraction with atropine or tetrodotoxin abolished the contractile response to electric field stimulation, indicating mediation via a cholinergic pathway. The adrenergic antagonists phentolamine and propranolol and the DA1 antagonist SCH 23390 were ineffective in antagonizing the action of dopamine. In contrast, the DA2 antagonist domperidone blocked the inhibitory effect of dopamine on electric field stimulation-mediated contractions. Schild analysis showed a Ki of 3 x 10(-8) mol/L and a slope of unity. In addition, it was shown that dopamine inhibited veratridine-evoked release of [3H]acetylcholine from the gastric myenteric plexus in a dose-related manner (median effective dose, 5.2 x 10(-5) mol/L). Tetrodotoxin abolished [3H]acetylcholine release evoked by veratridine, but hexamethonium had no effect. Domperidone, but not SCH 23390, antagonized the inhibitory action of dopamine. Pretreatment with pertussis toxin blocked the action of dopamine to inhibit evoked release of [3H]acetylcholine. These observations indicate that dopamine inhibits gastric muscle contraction evoked by electric field stimulation by inhibiting cholinergic transmission. This is mediated by DA2 receptors located on the postganglionic cholinergic neurons, and the pathway involves a pertussis toxin-sensitive G protein. The DA2-receptor antagonist domperidone antagonizes the inhibitory effect of dopamine, resulting in stimulation of gastric muscle contraction. This provides a mechanism for the gastrokinetic effect of domperidone.
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PMID:Mechanism for the gastrokinetic action of domperidone. In vitro studies in guinea pigs. 186 Jun 34

This study evaluates the involvement of GTP-dependent regulatory proteins (G-proteins) in the regulation of Na+-K+-ATPase activity in proximal convoluted tubule (PCT) segments. Single PCT segments were dissected from rat kidney and permeabilized to allow nucleotides and medium free access to the interior of the cell. A GDP analogue that blocks GTP-dependent activation of the G-protein, GDP beta S (400 microM) significantly inhibited PCT Na+-K+-ATPase activity when Na in the medium (Nam) was greater than or equal to 70 mM. The inhibition was attenuated when Nam was 55 and 35 mM and was no longer significant when Nam was 25 mM. GDP beta S had no inhibitory effect on the activity of purified Na+-K+-ATPase. A nonhydrolyzable GTP analogue, GppNHp (50 microM) significantly increased Na+-K+-ATPase activity when Nam was 25 and 35 mM, but not when Nam was 55-140 mM. Dopamine (DA) and DA1 plus DA2 agonists significantly inhibit Na+-K+-ATPase activity. DA inhibition was competitively abolished by GppNHp. In PCT segments from rats pretreated with pertussis toxin, DA and DA1 plus DA2 agonist inhibition of Na+-K+-ATPase activity was abolished. In PCT segments from rats pretreated with cholera toxin, basal Na+-K+-ATPase activity was increased, but DA significantly inhibited Na+-K+-ATPase activity. Na+-K+-ATPase activity in PCT segments is regulated via a G-protein that stimulates Na+-K+-ATPase activity and a DA-activated pertussis toxin-sensitive G-protein that inhibits Na+-K+-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of Na+-K+-ATPase activity in kidney proximal tubules: involvement of GTP binding proteins. 256 4

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

The involvement of dopamine (DA) receptor subtypes in regulation of renal phosphate transport by DA, either exogenous or locally synthesized from L-dihydroxyphenylalanine (L-dopa) was evaluated in opossum kidney (OK) cells with proximal tubular phenotype. DA synthesis from L-dopa by OK cells was abolished by carbidopa and benserazide, two dissimilar inhibitors of aromatic L-amino acid decarboxylase. L-Dopa stimulated cyclic AMP generation and inhibited Na-dependent Pi uptake, and these effects were abolished by carbidopa and benserazide. The effects of L-dopa or DA on cyclic AMP generation and on Na-Pi co-transport were mimicked by SKF 38393, a DA1 receptor agonist, and were potentiated by S-sulpiride, a DA2 receptor antagonist. Bromocriptine, a DA2 receptor agonist, blunted in a pertussis toxin-dependent manner parathyroid hormone (PTH)-induced cyclic AMP generation and inhibition of Pi uptake. In contrast with PTH, neither L-dopa nor DA affected significantly the cytosolic calcium concentration. These results support the involvement of DA1 and DA2 receptors, positively and negatively coupled into adenylate cyclase respectively, in modulation of renal phosphate transport.
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PMID:Locally formed dopamine modulates renal Na-Pi co-transport through DA1 and DA2 receptors. 852 52

The purpose of this study was to determine the mechanisms of dopamine regulation of phosphate uptake in opossum kidney (OK) cells, a model of proximal renal tubules. Dopamine stimulated cAMP generation and inhibited radiolabeled phosphate uptake into OK cell monolayers by 14.4 +/- 1.8%. The effect of dopamine was transient, as phosphate uptake returned toward control level by 3 h despite the continued presence of dopamine. Pretreatment with pertussis toxin increased dopamine inhibition of phosphate uptake to 25 +/- 3%, increased the duration of the dopamine effect to at least 3 h, and enhanced cAMP generation. In an OK cell clone that overexpressed cAMP phosphodiesterase, dopamine did not inhibit phosphate uptake, but pharmacologic inhibition of protein kinase A activation did not prevent dopamine inhibition of phosphate uptake. A DA1 receptor agonist inhibited phosphate uptake more potently than dopamine (29.5 +/- 1.1%) or a DA2 receptor agonist (7.9 +/- 2%). However, both DA1 and DA2 receptor antagonists completely blocked dopamine inhibition of phosphate uptake. DA1, but not the DA2, antagonists blocked dopamine-stimulated cAMP generation. Treatment with alpha-adrenergic receptor antagonists potentiated dopamine inhibition of phosphate uptake to the same extent as pertussis toxin and was not additive with pertussis toxin. It is concluded that dopamine inhibits phosphate uptake through DA1 and DA2 receptor stimulation by cAMP-dependent and -independent pathways and activates a pertussis toxin-sensitive counter-regulatory pathway that attenuates this response through alpha-adrenergic receptor stimulation.
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PMID:Dopamine regulates phosphate uptake by opossum kidney cells through multiple counter-regulatory receptors. 962 Dec 80