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)

Y-79 human retinoblastoma cells can be induced to express significant quantities of functional D2 dopamine receptors after attachment and differentiation with sodium butyrate. In membranes prepared from differentiated Y-79 cells, the D2 dopaminergic antagonist [3H] methylspiperone exhibits a KD of 77 pm and a Bmax of 60 fmol/mg of protein, whereas the antagonist [125I]iodosulpride reveals a KD of 0.77 nM and a Bmax of 40 fmol/mg of protein. Dopamine also induces a pharmacologically specific, pertussis toxin-sensitive, dose-dependent inhibition of forskolin-stimulated adenylyl cyclase activity, with an EC50 of 2 microM and a maximal response at 100 microM (approximately 50% enzyme inhibition). Pretreatment of the cells with dopamine results in a diminution in the subsequent ability of dopamine to inhibit adenylyl cyclase activity. This effect is time dependent, reaching maximal desensitization after approximately 24 hr. The dopamine dose-response curve for inducing desensitization exhibits an EC50 of approximately 2-3 microM and a maximal response at approximately 0.1-1 mM, similar to that for inhibiting adenylyl cyclase activity. After maximal desensitization, the EC50 for dopamine-induced inhibition of adenylyl cyclase activity is increased greater than 20 fold (lower affinity) and the maximum inhibition is decreased to approximately 15%, representing an approximately 70% desensitization. The agonist-induced desensitization is pharmacologically specific, inasmuch as preincubation of the cells with the dopaminergic agonists epinine and (+-)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene or the D2-selective agonist N-0434 also results in desensitization of dopamine-induced inhibition of enzyme activity, whereas preincubation with the D1-selective agonist SKF-38393 or with the nondopaminergic agonists isoproterenol and serotonin results in little or no desensitization. Preincubation of the cells with dopamine also promotes a time-dependent increase (approximately 3-fold) in the KD for [3H]methylspiperone, with no change in its Bmax. In contrast, after dopamine preincubation, the KD for [125I]iodosulpride is unchanged, whereas its Bmax is reduced by approximately 50% upon maximum desensitization. In addition, agonist pretreatment promotes a functional uncoupling of the D2 receptor, as suggested by a loss of high affinity agonist binding observed in radioligand competition binding assays after desensitization. Upon removal of agonist, the cellular D2 receptor binding activity and functional response recover to control levels within a 24-hr period. These results suggest that prolonged exposure of cells to dopaminergic agonists initiates a desensitization process involving a functional uncoupling of the D2 dopamine receptor as well as a loss of its ligand binding activity.
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PMID:Agonist-induced desensitization of D2 dopamine receptors in human Y-79 retinoblastoma cells. 167 85

Regulation of phosphate uptake was studied in HeLa cell lines after transfection with DNA encoding the human 5-HT1A receptor. Phosphate uptake was saturable and greater than 90% sodium-dependent, with Vmax approximately 30-35% without changing Km. Treatment with 5-HT or the 5-HT1A-specific agonist 8-OH-2-(di-n-propylamino)1,2,3,4-tetrahydronaphthalene increased Vmax approximately 40% without affecting Km. This effect was blocked by pretreatment with the 5-HT1 antagonists, methiothepine and spiperone, or pertussis toxin. Surprisingly, the stimulation was not secondary to an inhibition of adenylyl cyclase because 5-HT stimulated phosphate uptake approximately 20% in the presence of 1 mM 8-Br-cAMP. Rather, the primary pathway linked to the stimulation of phosphate uptake involved activation of protein kinase C because (i) 5-HT measurably activated protein kinase C in these cells, (ii) activators of protein kinase C (phorbol esters and diacylglycerol analogues) stimulated phosphate uptake in these cells (iii) the half-maximal doses for 5-HT-induced phosphatidylinositol hydrolysis and stimulation of phosphate uptake were virtually equivalent, and both effects were equally sensitive to pertussis toxin, and (iv) the stimulation was markedly attenuated in cells made deficient in protein kinase C. These results demonstrate that the stimulation of phosphatidylinositol hydrolysis by the 5-HT1A receptor can generate physiologically measurable effects on cellular transport and suggest that such accessory pathways may play a prominent role in signal transduction.
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PMID:The human 5-HT1A receptor expressed in HeLa cells stimulates sodium-dependent phosphate uptake via protein kinase C. 255 47

In synaptic plasma membranes of rat striatum, activation of dopamine receptors stimulates a high affinity GTPase activity. The rank order of potency of various dopamine receptor agonists in increasing GTP hydrolysis is the following: (-)-propylnorapomorphine greater than (-)-apomorphine = (+/-)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene [(+/-)-A-6,7-DTN] greater than dopamine = LY 171555 greater than noradrenaline. The selective D-1 dopamine receptor agonist, SKF 38393, does not produce a significant increase in GTP hydrolysis. Moreover, the dopamine-stimulated GTPase activity is completely reversed by the D-2 receptor antagonists, 1-sulpiride and zetidoline, but not by the selective D-1 antagonist SCH 23390. Na+ modulates the dopamine receptor-regulated GTP hydrolysis by increasing the percentage of stimulation and decreasing the agonist potency. Intrastriatal injection of pertussis toxin, which impairs the function of the inhibitory guanine nucleotide binding regulatory protein (Ni) of adenylate cyclase, significantly reduces the dopamine stimulation of striatal GTPase activity and the dopamine inhibition of adenylate cyclase. In contrast, cholera toxin, which blocks the stimulation of GTPase activity by hormones which increase adenylate cyclase activity, does not modify the dopamine-stimulated GTPase activity. These data indicate that the stimulation of GTPase activity elicited by dopamine results from activation of the D-2 type of dopamine receptors and is expression of the increased turnover of GTP at the level of Ni. The results are consistent with the idea that Ni is involved in the inhibitory coupling of striatal D-2 receptors to adenylate cyclase.
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PMID:Pharmacological and biochemical characterization of dopamine receptors mediating stimulation of a high affinity GTPase in rat striatum. 282 Apr 23

1. Dopaminergic transmission was investigated in the central nervous system (CNS) of the freshwater snail, Lymnaea stagnalis. 2. The giant pedal neuron, designated as right pedal dorsal one (RPeD1), makes chemical, monosynaptic connections with a number of identified follower cells in the CNS. Previous work has shown that RPeD1 is an interneuron and a important component of the Lymnaea respiratory central pattern generator. In this study, the hypothesis that RPeD1 uses dopamine as its neurotransmitter was tested by chromatographic, pharmacological, and electrophysiological methods. Characterization of RPeD1's transmitter pharmacology is essential to clearly understand its role in Lymnaea. 3. Earlier studies demonstrated that the soma of RPeD1 contains dopamine. This was quantitated in the present study by high-performance liquid chromatography (with electrochemical detection) of isolated RPeD1 somata and growth cones, which yielded 0.8 +/- 0.3 and 0.10 +/- 0.08 pmol of dopamine per soma and growth cone, respectively. 4. Bath or pressure application of dopamine to follower cells of RPeD1, in situ, mimicked the effects of RPeD1 stimulation. Dose-response curves were constructed for the excitatory effect of dopamine on follower cells, visceral dorsal two and three (VD2/3) (ED50 = 39 microM; Hill coefficient = 1.03), and the inhibitory effect of dopamine on follower cell, visceral dorsal four (ED50 = 33 microM; Hill coefficient = 0.92). 5. The following dopamine agonists (100 microM) were tested by bath application: 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN), apopmorphine, 2-bromo-alpha-ergocryptine, deoxyepinephrine (DE), mesulergine, (-) quinpirole, SKF 38393, and tyramine. Only the general dopamine agonists, ADTN and DE, mimicked RPeD1's effects on its follower cells. 6. When VD2/3 was isolated and plated in vitro, it maintained a depolarizing response to dopamine. This response was reduced by intracellular injection of the G-protein blocker, GDP-beta-S (2 mM in electrode). Similarly, incubation of VD2/3, in vitro for approximately 18 h, with pertussis toxin (PTX; 5 micrograms/ml), the G-protein inactivating exotoxin, also reduced the dopamine response. Injecting GDP or incubating in heat-inactivated PTX did not effect the response. 7. Several dopamine antagonists were used in an attempt to block RPeD1's synapses: chlorpromazine, ergonovine, fluphenazine, haloperidol, 6-hydroxydopamine, SCH 23390, (+/-) sulpiride, and tubocurarine. Only the D-2 dopamine receptor antagonist, (+/-) sulpiride, reversibly blocked synaptic transmission from RPeD1 to its follower cells. Both the (+) and the (-) enantiomer of sulpiride also antagonized synaptic transmission. A dose-inhibition curve for (+/-) sulpiride was constructed (IC50 = 47 microM).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dopaminergic transmission between identified neurons from the mollusk, Lymnaea stagnalis. 750 Jan 51

This study was conducted to determine the expression of dopamine D(2)-like receptors in opossum kidney (OK) cells and to examine the potential role of these receptors in mitogenesis. First, the presence of D(2)-like receptor binding sites in OK cell membranes was demonstrated by radioligand binding, using [(3)H]spiperone. The D(2)-like receptor subtypes expressed in OK cells were subsequently demonstrated, by Western blotting, to be D(2), D(3), and D(4) receptors. OK cells were stimulated with bromocriptine, (+/-)-2-(N-phenylethyl-N-propyl)amino-5-hydroxytetralin hydrochloride, (R)-(+)-2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide, or PD 168,077 maleate (D(2)-like, D(2), D(3), and D(4) receptor agonists, respectively), and mitogenesis was measured as a function of [(3)H]thymidine incorporation. It was observed that, whereas bromocriptine and (+/-)-2-(N-phenylethyl-N-propyl)amino-5-hydroxytetralin hydrochloride produced increases in [(3)H]thymidine incorporation, (R)-(+)-2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide and PD 168,077 maleate did not produce such an effect, indicating the involvement of D(2) receptors in the mitogenic response. Pertussis toxin and PD 98059 blocked the mitogenesis caused by bromocriptine, suggesting a role for G(i) or G(o) proteins and p44/42 mitogen-activated protein kinase (MAPK), respectively. Furthermore, it was observed that bromocriptine produced a time-dependent increase in the phosphorylation (activation) of p44/42 MAPK, which was blocked by domperidone, pertussis toxin, or PD 98059. Therefore, this study demonstrates that, although OK cells express D(2), D(3), and D(4) receptors, activation of only D(2) receptors causes mitogenesis via phosphorylation of p44/42 MAPK. Furthermore, the cellular mechanisms contributing to D(2) receptor-mediated phosphorylation of p44/42 MAPK seem to involve the tyrosine kinase, phosphatidylinositol-3-kinase, and protein kinase C pathways. It is likely that bromocriptine and other preferential D(2) receptor agonists might provide protection against ischemic reperfusion injury in renal proximal tubular cells, by increasing the survival rates for ischemic cells.
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PMID:Dopamine D(2) receptor activation causes mitogenesis via p44/42 mitogen-activated protein kinase in opossum kidney cells. 1151 77