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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

In this study, the regulation of striatal cyclic-3',5'-adenosine monophosphate (cAMP) formation and GABA release by dopamine D1 and metabotropic glutamate receptors (mGluR) was studied in brain slices. In the absence of adenosine A2 receptor blockade, the mGluR agonist, 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD) stimulated cAMP accumulation through a pertussis toxin-insensitive mechanism that could be blocked by L-serine-o-phosphate, but not by L(+)-2-amino-3-phosphonopropionic acid. However, in the presence of the adenosine antagonist, 3-isobutyl-1-methylxanthine, 1S,3R-ACPD had no significant effect on basal cAMP, but it inhibited cAMP formation stimulated by the D1 agonist, SKF 38393. This inhibitory response was prevented by pertussis toxin pretreatment and mimicked by L(+)-2-amino-3-phosphonopropionic acid, but it was unaffected by L-serine-o-phosphate. Thus, 1S,3R-ACPD was determined to activate distinct mGluRs in the striatum that mediate either inhibition or activation of cAMP accumulation, with the latter effect being dependent on the activation of adenosine A2 receptors. A potential physiological role for the interaction between the D1 and adenosine-dependent stimulatory metabotropic receptor was sought by examining this interaction on striatal GABA release. SKF 38393 and 1S,3R-ACPD together were found to potentiate striatal GABA release induced by 15 mM K+. The potentiation was blocked by the D1 antagonist, SCH 23390. However, this effect was only partially mimicked by a high concentration of forskolin (100 microM) and was not blocked by L-serine-o-phosphate, thereby suggesting that the stimulatory mGluR does not mediate this potentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of striatal cyclic-3',5'-adenosine monophosphate accumulation and GABA release by glutamate metabotropic and dopamine D1 receptors. 747 79

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

1. The effects of chronic in vitro administration of amitriptyline, a tricyclic antidepressant, on 5-hydroxytryptamine (5-HT) receptor-mediated adenylyl cyclase activity was studied in the neuroblastoma x glioma hybrid cell line, NG 108-15. 2. Treatment of NG 108-15 cells with 8 microM amitriptyline for 3 days increased forskolin-stimulated (0.1 microM) adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation. Addition of 5-HT (0.1-100 microM) increased forskolin-stimulated cyclic AMP accumulation in amitriptyline-treated cells in a concentration-dependent manner. However, 5-HT did not affect forskolin-stimulated cyclic AMP accumulation in untreated cells. 3. The 5-HT4 receptor agonist, 5-methoxytryptamine, significantly enhanced forskolin-stimulated cyclic AMP accumulation in amitriptyline-treated cells. In contrast, amitriptyline treatment failed to modify 8-hydroxy-2-(di-n-propylamine) tetralin-induced inhibition of forskolin-stimulated cyclic AMP accumulation. 4. Pretreatment of cells with pertussis toxin did not affect the 5-HT-induced enhancement of cyclic AMP accumulation. 5. The 5-HT-induced enhancement of cyclic AMP accumulation in amitriptyline-treated cells was attenuated by the 5-HT4 receptor antagonists, GR 113808 and ICS 205-930, with relatively low potency. However, spiperone, SCH 23390, and pindolol were completely ineffective against this 5-HT-induced enhancement. 6. Chronic treatment with amitriptyline did not modify the cyclic AMP production stimulated by prostaglandin E1 or cholera toxin. This treatment also had no effect on GTP gamma S-, NaF-, and Mn(2+)-stimulated cyclic AMP accumulation in isolated cell membranes. 7. Chronic treatment with the 5-HT receptor antagonists, pindolol or ICS 205-930, did not inhibit the 5-HT-induced enhancement of cyclic AMP accumulation.8. Chronic treatment with other antidepressant drugs, imipramine, mianserin or paroxetine, elicited the 5-HT-induced enhancement of cyclic AMP accumulation.9. Taken together, these results suggest that chronic amitriptyline treatment of NG 108-15 cells causes 5-HT to enhance forskolin-stimulated cyclic AMP accumulation by enhancing 5-HT receptor-mediated stimulation of adenylyl cyclase and not by reducing 5-HT-mediated inhibition of adenylyl cyclase. The 5-HT-induced enhancement of cyclic AMP accumulation in amitriptyline-treated cells may result from changes at the level of the 5-HT receptor rather than at the level of G, proteins or adenylyl cyclase. It is unlikely that this enhancement of cyclic AMP accumulation is caused by long-term antagonism of the 5-HT receptor by amitriptyline.
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PMID:Enhancement of cyclic AMP accumulation mediated by 5-HT after chronic amitriptyline treatment in NG 108-15 cells. 762 Jul 19

Iontophoresis of dopamine or the D1 agonist SKF 38393 has been shown to elicit current-dependent increases in the firing of rat substantia nigra pars reticulata neurons, suggesting a discrete physiological role for the D1 dopamine receptor population in the substantia nigra. The effects of SKF 38393 differed from those of dopamine, however, in that the D1 agonist also augmented inhibitory responses to applied GABA, whereas dopamine and D2-like agonists were previously found to attenuate responses to GABA. The present studies involved various manipulations of the nigral D1 receptors in order to examine the pharmacological specificity, receptor localization, and second messenger coupling underlying the D1 agonist response. The excitatory and GABA-potentiating effects of SKF 38393 were found to be attributable to D1 receptor stimulation, rather than a nonspecific action, since (1) the effect was mimicked by iontophoresis of A-68930, a D1 agonist of a different structural class than SKF 38393, and (2) the response to SKF 38393 was prevented by intranigral injection of the receptor inactivator N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ; 50 nmol/0.5 microliter) 1 d before, or the D1 antagonist SCH 23390 (1 microgram/microliter) 1 hr before electrophysiological testing. Additional studies revealed that the involved D1 receptors were located presynaptically on striatonigral terminals. For instance, in rats given ipsilateral striatal kainic acid lesions 1 week earlier, application of SKF 38393 failed to elicit the usual increases in cell firing, but loss of the response was observed only among the group of pars reticulata neurons that were shown to be unresponsive to striatal stimulation (i.e., those whose striatonigral inputs had been terminated by the lesion). Finally, to examine the second messenger coupling characteristics of the involved D1 receptors, several membrane-permeable analogs of cAMP were tested iontophoretically in place of SKF 38393. Surprisingly, none of these compounds gave a pattern of response typical of the D1 agonist, raising questions about the involvement of cAMP. Even more suggestive of an unconventional D1 coupling pathway, the excitatory and GABA-potentiating effects of applied SKF 38393 were completely abolished by prior intranigral injection of the G(i)/G(o) protein inactivator, pertussis toxin. Collectively, these results suggest that stimulation of D1 receptors on striatonigral terminals causes an excitation of substantia nigra pars reticulata neurons with an exaggerated responsiveness to GABA, and the effects appear to be mediated by a pertussis toxin-sensitive (i.e., a non-G-like) G-protein and possibly a second messenger other than cAMP.
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PMID:D1 agonist-induced excitation of substantia nigra pars reticulata neurons: mediation by D1 receptors on striatonigral terminals via a pertussis toxin-sensitive coupling pathway. 791 24

Dopamine neurons derived from the mesencephalon of embryonic rats were maintained in primary culture, identified and studied with whole-cell patch recording techniques. These neurons demonstrated a rapidly activating and inactivating voltage-dependent outward current which required the presence of K+ ions. This current was termed IA because of its transient nature. It was elicited by step depolarizations from holding potentials more negative than -50 mV and exhibited steady-state inactivation at a membrane potential more positive than -40 mV and half-maximal inactivation observed at -65 mV. This current rapidly achieved peak activation in less than 8 msec and decayed with a time constant (tau) of 58 +/- 5 msec. This current was observed in the presence of tetraethylammonium but was readily blocked by 4-aminopyridine (2-4 mM). This current was also observed to be modulated by stimulation of D2 dopamine receptors (DA autoreceptors) located on the dopamine neurons. Thus, both DA and the D2 receptor agonist quinpirole enhanced the peak IA observed, while the partial D1 receptor agonist SKF 38393 was without effect. The enhancement of IA was confirmed to be due to the activation of D2 receptors as the effects of either DA or quinpirole were blocked by the D2 receptor antagonists eticlopride and sulpiride, but not by the D1 receptor antagonist SCH 23390. Since we have previously demonstrated that the IK present in these cells is also enhanced by D2 receptor stimulation, we investigated the signal transduction pathways involved in coupling DA autoreceptors to both IA and IK. The response of both these potassium currents to DA autoreceptor stimulation was completely abolished by the preincubation of cultures with pertussis toxin, indicating the possible involvement of the G proteins Gi and G(o). In an attempt to further characterize which G protein may be involved, additional experiments were performed. The ability of DA autoreceptor stimulation to augment both currents was also blocked completely when G protein activation was prevented by the intracellular application of GDP beta S (100 microM). In contrast, irreversible activation of G proteins by intracellular application of the nonhydrolyzable GTP analog GTP gamma S (100 microM) mimicked the effects of DA autoreceptor stimulation on both IA and IK. In addition, the intracellular application of a polyclonal antibody that was selective for the alpha-subunit of G(o) completely abolished the DA autoreceptor modulation of both currents while preimmune serum was without effect.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dopamine neuron membrane physiology: characterization of the transient outward current (IA) and demonstration of a common signal transduction pathway for IA and IK. 799 98

K(+)-evoked acetyl[3H]choline ([3H]ACh) release was inhibited in a concentration-dependent manner by apomorphine and the D2 agonist quinpirole in striatal slices prepared from euthyroid and hypothyroid rats. However, there was a significant increase in the maximum inhibition observed with both agonists in the hypothyroid compared with the euthyroid group, which paralleled the increased D2 agonist sensitivity reported for stereotyped behavior. The D2 antagonist raclopride decreased, and the D1 antagonist SCH 23390 increased, the inhibition of [3H]ACh release by apomorphine, confirming an inhibitory role for D2 receptors and an opposing role for D1 receptors. Because there is no difference in D1 or D2 receptor concentration between the euthyroid and hypothyroid groups, it is suggested that thyroid hormone modulation of D2 receptor sensitivity affects a receptor-mediated event. Following intrastriatal injection of pertussis toxin (PTX), apomorphine no longer inhibited [3H]ACh release. In fact, increased [3H]-ACh release was observed, an effect reduced by SCH 23390, providing evidence that D1 receptors enhance [3H]-ACh release, and confirming that a PTX-sensitive G protein mediates the D2 response. As it has been reported that thyroid hormones modulate G protein expression, this mechanism may underlie their effect on dopamine agonist-mediated inhibition of ACh.
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PMID:Dopamine agonist-mediated inhibition of acetylcholine release in rat striatum is modified by thyroid hormone status. 810 83

Although it is suspected that dopamine (DA) inhibits a Ca++ current in sympathetic neurons, the receptor and the Ca++ channel type involved are still unknown. We found that DA caused a reversible inhibition on omega-conotoxin sensitive and resistant Ca++ currents in the superior cervical ganglion (SCG). The concentration of DA that induced half-maximal inhibition was 3.0 microM. The DA receptor agonists (+/-)-SKF-38393 (D1 type) and quinpirole (D2 type) appeared unable to induce an inhibition of the Ca++ current. Furthermore, the receptor antagonists SCH-23390 (D1 type) and (-)-sulpiride (D2 type) did not prevent the inhibitory effect of DA. This suggests that the effect of DA on the Ca++ current was not due to activation of DA receptors. The inhibition of the Ca2++ current by DA was reduced by application of 1 microM phentolamine, a nonselective alpha adrenergic antagonist, and by prazosin and yohimbine, alpha-1 and alpha-2 receptor antagonists, respectively. The beta adrenergic receptor antagonist propranolol did not block the effect of DA. A guanine nucleotide-binding protein appears to be involved in the activation of adrenergic receptors by DA. The addition of GTP-gamma-S (0.1 mM) to the intracellular solution produced an effect similar to that of DA. Incubation of sympathetic neurons with pertussis toxin reduced the effect of DA by 90%. The results indicate that DA reduces the number of available Ca++ channels in sympathetic neurons by activation of alpha adrenergic receptors, which are associated with a pertussis-sensitive GTP-binding protein.
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PMID:Dopamine inhibits a sustained calcium current through activation of alpha adrenergic receptors and a GTP-binding protein in adult rat sympathetic neurons. 818 18

Two isoforms of the D2 dopamine receptor exist, termed D2 short (D2s) and D2 long, which differ by the presence or absence of 29 amino acids. To examine the possible coupling of the D2s isoform to voltage-dependent K+ current, NG108-15 cells that were transfected with and stably express this isoform were studied using whole-cell patch-clamp techniques. In transfected, but not untransfected, cells dopamine and quinpirole (QUIN) reduced the normally observed peak outward K+ current, and this effect was abolished by the D2 antagonist sulpiride but not by the alpha 2-adrenergic receptor antagonist idazoxan or the D1 antagonist (R)-(+)-SCH-23380. The D1 receptor agonist SKF 38393 had no effect. QUIN-induced inhibition of K+ current was prevented by loading the cells with the Ca(2+)-chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, suggesting a critical role for intracellular Ca2+ mobilization. In contrast, reduction of the concentration of extracellular Ca2+ and inclusion of the Ca2+ channel blocker cobalt did not modify the reduction of K+ current produced by stimulation of D2s receptors. A critical role for intracellular calcium mobilization in the observed effects was further supported by the observation that increases in cytosolic Ca2+ produced by thapsigargin mimicked the effect of QUIN, whereas intracellular ryanodine, which blocks Ca2+ mobilization, abolished the QUIN responsiveness. Finally, the effect of D2S activation on K+ current was not modified by pretreatment of the cells with pertussis toxin. These results suggest that the D2s dopamine receptor expressed in NG108-15 cells inhibits the activity of native K+ current via a mechanism that is dependent upon the mobilization of intracellular Ca2+ and does not involve a pertussis toxin-sensitive G protein.
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PMID:Transfected D2 short dopamine receptors inhibit voltage-dependent potassium current in neuroblastoma x glioma hybrid (NG108-15) cells. 837 17

1. Inhibition by haloperidol and chlorpromazine of a voltage-activated K+ current was characterized in rat phaeochromocytoma PC12 cells by use of whole-cell voltage-clamp techniques. 2. Haloperidol or chlorpromazine (1 and 10 microM) inhibited a K+ current activated by a test potential of +20 mV applied from a holding potential of -60 mV. The K+ current inhibition did not exhibit voltage-dependence when test potentials were changed between -10 and +40 mV or when holding potentials were changed between -120 and -60 mV. 3. Effects of compounds that are related to haloperidol and chlorpromazine in their pharmacological actions were examined. Fluspirilene (1 and 10 microM), an antipsychotic drug, inhibited the K+ current, but pimozide (1 and 10 microM), another antipsychotic drug did not significantly inhibit the K+ current. Sulpiride (1 or 10 microM), an antagonist of dopamine D2 receptors, did not affect the K+ current whereas (+)-SCH-23390 (10 microM), an antagonist of dopamine D1 receptors, reduced the K+ current. As for calmodulin antagonists, W-7 (100 microM), but not calmidazolium (1 microM), reduced the K+ current. 4. The inhibition by haloperidol or chlorpromazine of the K+ current was abolished when GTP in intracellular solution was replaced with GDP beta S. Similarly, the inhibition by pimozide, fluspirilene, (+)-SCH-23390 or W-7 was abolished or attenuated in the presence of intracellular GDP beta S. The inhibition by haloperidol or chlorpromazine was not prevented when cells were pretreated with pertussis toxin or when K-252a, an inhibitor of a variety of protein kinases, was included in the intracellular solution. 5. Haloperidol and chlorpromazine reduced a Ba2+ current permeating through Ca2+ channels. Inhibition by haloperidol or chlorpromazine of the Ba2+ current was not affected by GDP beta S included in the intracellular solution. 6. It is concluded that haloperidol and chlorpromazine inhibit voltage-gated K+ channels in PC12 cells by a mechanism involving GTP-binding proteins. The inhibition may not be related to their activity as antagonists of dopamine D2 receptors or calmodulin antagonists.
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PMID:Characterization of inhibition by haloperidol and chlorpromazine of a voltage-activated K+ current in rat phaeochromocytoma cells. 859 Sep 77


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