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

We have examined the cross talk between adenosine and bradykinin receptors in DDT1 MF-2 smooth muscle cells. Both adenosine and bradykinin mobilized intracellular free calcium via the formation of inositol 1,4,5-trisphosphate in a time- and dose-dependent manner. Adenosine exerted its actions via adenosine A1 receptors as demonstrated by the observations that N6-cyclopentyladenosine, a selective A1 receptor agonist, had an EC50 in the low nanomolar range and that a selective adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine, counteracted adenosine-mediated responses at concentrations typical for signaling via adenosine A1 receptors. Adenosine A1 receptors were coupled to phospholipase C via pertussis toxin-sensitive guanine nucleotide-binding regulatory protein(s) [G protein(s)], whereas bradykinin responses were unaffected by pertussis toxin. When adenosine or N6-cyclopentyladenosine was combined with bradykinin, the resulting formation of inositol 1,4,5-triphosphate was more than additive, and the EC50 value for adenosine and N6-cyclopentyladenosine was shifted to the left by bradykinin, the affinity of which was unaltered. Combining N6-cyclopentyladenosine and bradykinin also synergistically raised intracellular free calcium both at subthreshold levels and at maximal concentrations of the two agonists. The interaction was not dependent upon cAMP. In conclusion, stimulation of adenosine A1 receptors coupled to pertussis toxin-sensitive G protein(s) and bradykinin receptors coupled to pertussis toxin-insensitive G protein(s) synergistically mobilizes intracellular free calcium and inositol 1,4,5-trisphosphate formation.
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PMID:Stimulation of adenosine A1 receptors and bradykinin receptors, which act via different G proteins, synergistically raises inositol 1,4,5-trisphosphate and intracellular free calcium in DDT1 MF-2 smooth muscle cells. 132 31

The purpose of the present study was to investigate the contribution of pertussis toxin (PTX)-sensitive guanine nucleotide (G) proteins in the pulmonary vascular response to adenosine and ATP in the intact cat under conditions of controlled pulmonary blood flow and left atrial pressure. Adenosine, ATP, and beta-tau-ATP increased lobar arterial pressure in a dose-dependent manner. The pulmonary vasoconstrictor response to adenosine was abolished by BW 1433U, a specific purinergic receptor (P1) inhibitor, PTX pretreatment, indomethacin, and ONO 3708, a thromboxane A2 (TxA2) receptor antagonist. These data suggest that the pulmonary vasoconstrictor response to adenosine depends on activation of P1 purinergic receptors coupled to PTX-sensitive G proteins and subsequent metabolism of liberated arachidonic acid to form TxA2. Because each blocking agent studied produced similar reductions in the pulmonary vasoconstrictor response to ATP without altering the pulmonary vasoconstrictor response to beta-tau-ATP, the present data suggest that ATP constricts the pulmonary vascular bed, in part, by hydrolysis to adenosine. Moreover, the present study suggests that both A1 purinoceptors that are linked to PTX-sensitive G proteins as well as P2x purinoceptors receptors that are independent of PTX-insensitive G proteins mediate the pulmonary vasoconstrictor response to ATP in vivo.
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PMID:Mechanisms of signal transduction for adenosine and ATP in pulmonary vascular bed. 134

Intracellular and voltage-clamp recordings were made from neurons in rat brain slices containing dorsolateral septal nucleus (DLSN), in vitro. Bath application of adenosine (100 microM) produced a hyperpolarization (2-15 mV) in 46% of DLSN neurons (AH-neurons); in the remaining 54% neurons (non-AH-neurons), no hyperpolarization to adenosine was observed. Adenosine (1-300 microM) depressed not only the excitatory postsynaptic potential (EPSP) but also the inhibitory postsynaptic potential (IPSP) and the late hyperpolarizing potential (LHP) evoked by stimulation of the hippocampal CA3 area or the fimbria/fornix pathway in both AH- and non-AH-neurons. In non-AH-neurons, adenosine did not block current responses resulting from glutamate, muscimol or baclofen applied directly to DLSN neurons. In AH-neurons, adenosine partially depressed the baclofen-induced outward current. Adenosine did not block the directly-evoked IPSP (monosynaptic IPSP) as well as the glutamate-induced (hyperpolarizing) postsynaptic potential (PSP) that is mediated by GABA released from interneurons. These results suggest that adenosine does not directly inhibit the release of GABA. The effects of adenosine was mimicked by selective A1-receptor agonists and was blocked by selective A1-receptor antagonists. Pertussis toxin (PTX) blocked the hyperpolarization induced by adenosine or baclofen applied exogenously. Adenosine consistently produced presynaptic inhibition of the EPSP even in DLSN neurons treated with PTX. We conclude that adenosine inhibits neurotransmission between the hippocampus and septum through activation of pre- and postsynaptic A1-receptors which couple with G-proteins of different PTX-sensitivity or with distinct transduction processes at pre- vs. postsynaptic sites.
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PMID:Adenosine inhibits the synaptic potentials in rat septal nucleus neurons mediated through pre- and postsynaptic A1-adenosine receptors. 135 69

1. Intracellular microelectrode recordings were used to study the cellular location, the receptor pharmacology, and the mechanism of action of adenosine on pyramidal cells and presynaptic axonal endings in area CA3 of organotypic hippocampal slice cultures. 2. Adenosine (bath applied at 50 microM) caused a 10-15 mV hyperpolarization of CA3 cells, as well as a 75-100% decrease in the amplitude of excitatory and polysynaptic inhibitory postsynaptic potentials (EPSPs and IPSPs). Adenosine had no effect on the amplitude of monosynaptic IPSPs elicited in the presence of excitatory amino acid receptor antagonists, but did reduce the amplitude of isolated EPSPs, elicited after blocking GABAA receptors and reducing subsequent epileptic bursts with excitatory amino acid receptor antagonists. These data indicate that adenosine receptors are located on excitatory, but not inhibitory, presynaptic elements. 3. The A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, bath applied at 200 nM) blocked the pre- and postsynaptic actions of adenosine. DPCPX had no effect on the amplitude of control synaptic responses, suggesting that there is no tonic activation of adenosine receptors in hippocampal slice cultures under control conditions. The A1 receptor agonists R-N6-phenylisopropyladenosine (R-PIA) mimicked all pre- and postsynaptic actions of adenosine. 4. Pertussis toxin pretreatment (500 ng/ml for 48 h) prevented adenosine from activating postsynaptic K+ conductance, but not from inhibiting EPSPs. In contrast, stimulation of protein kinase C with phorbol ester (phorbol 12, 13-dibutyrate, 1 microM for 10 min) reduced the presynaptic, but not the postsynaptic, actions of adenosine. 5. Barium (bath applied at 1 mM) blocked the adenosine-activated K+ conductance, but not the inhibition of isolated EPSPs by adenosine. 6. Adenosine at 0.03-1 microM reduced the frequency of, or blocked, spontaneous epileptiform bursting produced by bicuculline. DPCPX (200 nM) increased the rate of spontaneous bursting, consistent with a tonic activation of adenosine receptors during hyperactivity, and led to the development of prolonged ictal-like bursts, suggesting that the endogenous release of adenosine may contribute to the termination of epileptic bursts. 7. We conclude that adenosine acts at pre- and postsynaptic receptors which are pharmacologically indistinguishable. Postsynaptically, adenosine increases a barium-sensitive K+ conductance via a pertussis toxin-sensitive GTP-binding protein. The presynaptic action of adenosine must, however, be mediated by some other mechanism.
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PMID:Comparison of the actions of adenosine at pre- and postsynaptic receptors in the rat hippocampus in vitro. 140 15

This study examines the cellular basis and specificity of the effects of adenosine on early afterdepolarizations (EADs), delayed afterdepolarizations (DADs), and triggered activity (TA) induced by various drugs with different mechanisms of action. Membrane potential and currents were measured in isolated guinea pig ventricular myocytes. Adenosine (10-100 microM) significantly (p less than 0.05) reduced the amplitude of DADs and suppressed TA induced by isoproterenol (10-50 nM) and forskolin (1 microM) but not those induced by dibutyryl cAMP (1 microM), ouabain (1-5 microM), and 7.2 mM [Ca2+]o. Adenosine also abolished EADs and TA induced by isoproterenol. In contrast, adenosine failed to abolish EADs and TA induced by quinidine (3 microM) or those that occurred spontaneously (i.e., in the absence of drugs). Transient inward current (ITi) was induced on repolarization after 2-second-long single depolarizing voltage steps or after 12-second-long trains of 300-msec depolarizing pulses. Concomitant with the attenuation of DADs, adenosine suppressed ITi caused by isoproterenol and forskolin but not those induced by ouabain, dibutyryl cAMP, and elevated [Ca2+]o. The amplitude of ITi was dependent on the magnitude of the activating voltage step, but the suppression of ITi by adenosine was not. The selective A1-adenosine receptor antagonist N-0861 (9-methyladenine derivative) antagonized the effects of adenosine on afterdepolarizations, ITi, and TA. In myocytes from guinea pigs treated with pertussis toxin, adenosine failed to attenuate DADs and ITi or abolish TA induced by isoproterenol or forskolin. In parallel experiments, isoproterenol (10 nM) raised cellular cAMP from 5.7 +/- 0.2 to 8.1 +/- 0.1 pmol and the selective A1 receptor agonist cyclopentyladenosine (5 microM) reduced it to 6.5 +/- 0.2 pmol (p less than 0.05). Thus, adenosine specifically attenuates afterdepolarizations and abolishes TA by suppressing ITiS that are associated with stimulation of adenylate cyclase via a pertussis toxin-sensitive A1 receptor-mediated action. In conclusion, the response of TA to adenosine may identify a mechanism of afterdepolarization related to stimulation of adenylate cyclase.
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PMID:Adenosine-sensitive afterdepolarizations and triggered activity in guinea pig ventricular myocytes. 155 Dec

The effect of adenosine on phosphoinositide hydrolysis was examined in 1321N1 human astrocytoma cells. Adenosine, L-N6-phenylisopropyladenosine (L-PIA), and 5'-(N-ethylcarboxamido)adenosine (NECA) inhibited histamine-stimulated accumulation of inositol phosphates in a concentration-dependent manner. The potency order of adenosine analogues for inhibition of inositol phosphate accumulation was L-PIA greater than adenosine greater than NECA, a finding indicating that A1-class adenosine receptors are involved in the inhibition. The reduction in inositol phosphate accumulation by L-PIA was blocked by an adenosine receptor antagonist, 8-phenyltheophylline. Stimulation of A1-class adenosine receptors inhibited isoproterenol-stimulated cyclic AMP accumulation as well as histamine-induced inositol phosphate accumulation. Both inhibitory effects were blocked by pretreatment of the cells with pertussis toxin [islet-activating protein (IAP)]. L-PIA also inhibited guanosine 5'-(gamma-thio)triphosphate (GTP gamma S)-stimulated accumulation of inositol phosphates in membrane preparations, and 8-phenyl-theophylline antagonized the inhibition. L-PIA could not inhibit GTP gamma S-induced accumulation of inositol phosphates in IAP-treated membranes. Gi/Go, purified from rabbit brain, inhibited GTP gamma S-stimulated accumulation of inositol phosphates in a concentration-dependent manner in membrane preparations. These results suggest that stimulation of A1-class adenosine receptors interacts with the IAP-sensitive G protein(s), resulting in the inhibitions of phospholipase C as well as adenylate cyclase in human astrocytoma cells.
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PMID:Adenosine inhibits histamine-induced phosphoinositide hydrolysis mediated via pertussis toxin-sensitive G protein in human astrocytoma cells. 165 Mar 98

1. After blocking K+ currents with 10 mM-tetraethylammonium (TEA) or TEA plus 250 microM-3,4-diaminopyridine (3,4-DAP). motor nerve terminal Ca2+ currents were recorded using focal extracellular electrodes. Two transmitters released from the terminal. ATP and acetylcholine (ACh), were then applied, and the effects on the nerve terminal Ca2+ current were measured. 2. ATP (50 microM) reduced the Ca2+ current by 34%, but this action is prevented when hydrolysis to adenosine is blocked by alpha,beta-methyladenosine 5'-diphosphate (200 microM). Thus, inhibition by ATP presumably occurs subsequent to ATP hydrolysis to adenosine. 3. Adenosine (50 microM) inhibited the terminal Ca2+ current by 29%. This was mimicked by the adenosine analogue L-phenylisopropyl adenosine (L-PIA) and blocked by theophylline (100 microM), which antagonizes adenosine receptors at micromolar concentrations. 4. ACh (100 microM) or the anticholinesterase methane sulphonyl fluoride (MSF; 1 mM) also depressed the terminal Ca2+ current. This response was mimicked by muscarine (100 microM) and antagonized by atropine (100 microM) or pirenzipine (4 microM), which is generally specific for M1 receptors. 5. Addition of Ba2+, which blocks adenosine-mediated K+ currents, had no effect on the inhibitory effects of either adenosine or ACh; similarly, neither adenosine nor ACh in the bath affected K+ current records obtained after blocking all inward currents with 10 mM-Co2+ and focal application of tetrodotoxin. 6. Incubation of the muscle for 4 h in pertussis toxin (10(-5) g ml-1) eliminated both adenosine- and ACh-induced inhibition of the terminal Ca2+ current. This result indicates the possible involvement of a G protein in the transduction of the feedback pathway. 7. Neither cyclic AMP analogues, the adenylate cyclase activator forskolin (10 microM), the phorbol ester phorbol 12-myristate 13-acetate (PMA; 3 microM) nor the diacylglycerol analogue 1,2-oleoylacetylglycerol (OAG; 3 microM) had any effect on adenosine- or ACh-induced depression of the terminal Ca2+ current. Therefore, pathways involving these particular second messengers are most probably not involved. 8. The effects of adenosine and ACh are non-additive. 9. These results indicate that ATP and ACh, which are released during exocytosis, may inhibit their own release through attenuation of the terminal Ca2+ current via autoreceptors coupled to a G protein.
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PMID:Autoreceptor-mediated purinergic and cholinergic inhibition of motor nerve terminal calcium currents in the rat. 165 22

Adenosine contracts pregnant and nonpregnant guinea pig myometrial smooth muscle (MSM). We have 1) described dissociation of A1-adenosine receptors from adenylate cyclase inhibition in nonpregnant MSM (M. A. Smith, J. L. Silverstein, D. P. Westfall, and I. L. O. Buxton, Cell. Signal. 1: 357-365, 1989); 2) described appearance of such inhibitory coupling in pregnant MSM [W. P. Schiemann, D. P. Westfall, and I. L. O. Buxton, Am. J. Physiol. 261 (Endocrinol. Metab. 24): E141-E150, 1991]; and 3) demonstrated a role for myometrial A1 receptors in the rapid formation of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in nonpregnant MSM and the cyclooxygenase dependence of this effect (W. P. Schiemann, K. O. Doggwiller, and I. L. O. Buxton. J. Pharmacol. Exp. Ther. 258: 429-437, 1991). To further characterize adenosine action in pregnant tissue, we explored A1 coupling to increased phosphoinositide hydrolysis in near-term pregnant MSM. The A1-receptor agonist (+)-N6-(2-phenylisopropyl)adenosine stimulates the rapid dose-dependent formation of Ins(1,4,5)P3 and stimulates rapid degradation of uterine inositol monophosphates (InsP) in a manner paralleling increases in inositol polyphosphates. Both A1-mediated responses were blocked by the A1 antagonist 8-(p-sulfophenyl)theophylline, and, unlike the effect observed in nonpregnant MSM, treatment of pregnant MSM with either meclofenamate or indomethacin failed to block A1-mediated increases in Ins(1,4,5)P3. Pretreatment of MSM with either Li+ or pertussis toxin failed to alter either Ins(1,4,5)P3 formation or InsP degradation. Furthermore, assay of inositol phosphomonoesterase (InsPase) activity in the presence or absence of Li+ confirmed the existence of an MSM Li(+)-insensitive InsPase enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine A1-receptor coupling to phosphoinositide metabolism in pregnant guinea pig myometrium. 165 16

1. The role of adenosine receptors in reducing calcium currents (ICa) and in triggering presynaptic inhibition was studied using whole-cell patch-clamp techniques to record ICa and synaptic currents from the cell bodies of cultured rat hippocampal pyramidal neurones. Recordings of intracellular Ca2+ using the indicator dye Fura-2 were used to obtain further insights into the actions of adenosine agonists. 2. The adenosine analogue 2-chloroadenosine (2-CA) reduced ICa in these neurones. This action was also evident when Ba2+ was used as the charge carrier through Ca2+ channels. Adenosine also reduced the influx of Ca2+ into the cell body during a depolarizing voltage-clamp pulse as measured with Fura-2. The potency of various adenosine receptor agonists was as follows: cyclopentyladenosine greater than cyclohexyl-adenosine greater than or equal to R-phenylisopropyladenosine greater than 2-CA greater than S-phenylisopropyladenosine, consistent with the pharmacological profile of an A1 adenosine receptor. 3. The specific A1 receptor antagonist cyclopentyltheophylline (CPT) blocked the actions of 2-CA on ICa in a competitive fashion. 4. The actions of 2-CA on ICa were abolished by pre-incubation of cultured cells with pertussis toxin (PTX; 250 ng/ml). Intracellular dialysis with the GTP analogue GTP-gamma-S (guanosine-5'-O-(3-thiotriphosphate] enhanced the actions of 2-CA and rendered the response irreversible. 5. Excitatory postsynaptic currents (EPSCs) were recorded from pyramidal neurones under whole-cell voltage clamp by stimulating nearby neurones with an extracellular electrode. 2-CA potently and reversibly reduced the amplitude of EPSCs. This action was shown to be due to presynaptic inhibition of neurotransmitter release. 6. The order of potency of different adenosine agonists in reducing EPSCs was as follows: cyclopentyladenosine greater than cyclohexyladenosine greater than or equal to R-phenylisopropyladenosine greater than 2-CA greater than S-phenylisopropyladenosine. CPT inhibited the action of 2-CA in a competitive fashion. 7. The effects of 2-CA on synaptic transmission were abolished by pre-treatment with 250 ng/ml PTX, indicating that a PTX-sensitive G-protein is involved in this action. 8. These results indicate that activation of adenosine receptors does induce a reduction in ICa in hippocampal pyramidal neurones. Furthermore, this effect and the reduction of excitatory synaptic transmission by adenosine analogues are both mediated by PTX-sensitive G-proteins and have identical pharmacological properties.
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PMID:Analysis of adenosine actions on Ca2+ currents and synaptic transmission in cultured rat hippocampal pyramidal neurones. 166 61

When applied extracellularly in the micromolar range, ATP and related compounds induced a positive inotropy in the rat papillary muscle. This was also true in the rat auricle after pertussis toxin treatment. Then, in both tissues, ATP further increased the contraction after a maximal beta-adrenergic stimulation. The increase in contractile force could be related to the increase in the calcium current. The L-type calcium current was measured by whole-cell patch-clamp recording in single cells isolated from the rat ventricle after the sodium and potassium currents were inhibited by tetrodotoxin and cesium, respectively. When added alone, 10 microM ATP increased the calcium current by 60%. Adenosine 5'-O-(3-thiotriphosphate) was also able to increase calcium current. Adenosine was much less effective, and GTP, UTP, CTP, and ITP were without effect. A similar increase in calcium current was observed when ATP was added in addition to a maximal stimulation by a beta-adrenergic agonist or after internal perfusion with cyclic AMP. However, this increase was preceded by a transient decrease whose origin could not be attributed to a P1-purinergic agonistic effect of ATP. The transient decrease was not elicited by adenosine or in a magnesium-free HEPES solution and was not suppressed after pertussis toxin treatment. This effect appeared related to the variations in the holding current also observed upon ATP application. Together with vasodilation, ATP and adenine compounds induced positive inotropy. The latter effect could be attributed in part to the increase in calcium current and was independent of cyclic AMP. Both effects are complementary with the beta-adrenergic stimulation and can help healthy cells to compensate the failing zone from which ATP could be released.
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PMID:The mechanism of positive inotropy induced by adenosine triphosphate in rat heart. 169 71


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