Reduction by intracellular calcium chelation of acetylcholine secretion without occluding the effects of adenosine at frog motor nerve endings

Hunt, James M.; Redman, R. S.; Silinsky, Eugene M.

doi:10.1111/j.1476-5381.1994.tb14802.x

Cited by 13 publications

(10 citation statements)

References 26 publications

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“…First, STDs are unlikely to be of neurogenic origin as they were not inhibited by atropine, phentolamine, guanethidine or tetrodotoxin. Most importantly they were abolished by BAPTA/ AM indicating that they are not due to spontaneous release of transmitter which, as shown in studies on other tissues, is not inhibited by chelation of [Ca2+]i (e.g., Hunt et al, 1994). Indeed reduction by BAPTA/AM coupled with findings of partial or complete inhibition by nominally Ca2" free solution, CPA, procaine and caffeine of both STDs and SWs, indicates that both arise through release of Ca2" from intracellular stores.…”

Section: Discussionmentioning

confidence: 56%

“…First, STDs are unlikely to be of neurogenic origin as they were not inhibited by atropine, phentolamine, guanethidine or tetrodotoxin. Most importantly they were abolished by BAPTA/ AM indicating that they are not due to spontaneous release of transmitter which, as shown in studies on other tissues, is not inhibited by chelation of [Ca2+]i (e.g., Hunt et al, 1994 (Siedler et al, 1989;Uyama et al, 1992). Procaine inhibits the release of Ca21 from store sites, by preventing Ca2+-induced Ca2+-release (CICR; Itoh et al, 1981).…”

Section: Discussionmentioning

confidence: 87%

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Properties of spontaneous depolarizations in circular smooth muscle cells of rabbit urethra

Hashitani

Helden

Suzuki

1996

British J Pharmacology

126

140

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. Intracellular microelectrode recordings were made from circular smooth muscle of rabbit urethra. . The smooth muscle of urethra was spontaneously active exhibiting large, regularly occurring depolarizations, termed slow waves (SWs), 1–3 s in duration, up to 40 mV in amplitude and generated every 3–15 s and small irregularly occurring events (or summations there of) termed spontaneous transient depolarizations (STDs) of < 1 s in duration. . The SWs and STDs were not sensitive to 10−6 m atropine, 10−6 m phentolamine, 10−5 m guanethidine or 10−6 m tetrodotoxin, indicating that they were myogenic in origin. . Application of 3 × 10−6 m nifedipine or 5 × 10−5 m GdCl3 did not inhibit the generation of SWs or STDs, indicating that activation of L‐type Ca2+ channels and non‐selective cation channels are not essential for their generation. However, the duration of SWs but not STDs was reduced by nifedipine, indicating L‐type Ca2+ channels contribute to the plateau‐like potential of SWs. . Application of low chloride solution (6.4 mM), niflumic acid (10−5‐10−4 m) or 4,4′‐diisothiocyanostilbene‐2,2′‐disulphonic acid (DIDS, 10−4‐5 × 10−4 m) inhibited the generation of SWs and STDs, suggesting an involvement of chloride channels. . Application of nominally Ca2+ free solution, 5 × 10−5 m BAPTA‐AM, 10−5 m cyclopiazonic acid, 10−2 m caffeine or 10−3 m procaine inhibited the generation of SWs and STDs, indicating that Ca2+ released from intracellular stores was required for the generation of SWs and STDs. . Exogenously applied noradrenaline (10−7‐10−5 m) increased the frequency of SWs through stimulation of α‐adrenoceptors which was inhibited by sodium nitroprusside (SNP, 10−4 m). SNP also reduced the frequency of SWs without altering the membrane potential, an effect mimicked by 8‐bromocyclic GMP (10−3 m) indicating that SNP acted by elevating the production of cyclic GMP. . It is concluded that smooth muscle cells of the rabbit urethra exhibit SWs and STDs which are likely to be induced by stimulation of Ca2+‐activated chloride channels evoked by release of Ca2+ from intracellular stores.

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Section: Discussionmentioning

confidence: 56%

“…First, STDs are unlikely to be of neurogenic origin as they were not inhibited by atropine, phentolamine, guanethidine or tetrodotoxin. Most importantly they were abolished by BAPTA/ AM indicating that they are not due to spontaneous release of transmitter which, as shown in studies on other tissues, is not inhibited by chelation of [Ca2+]i (e.g., Hunt et al, 1994 (Siedler et al, 1989;Uyama et al, 1992). Procaine inhibits the release of Ca21 from store sites, by preventing Ca2+-induced Ca2+-release (CICR; Itoh et al, 1981).…”

Section: Discussionmentioning

confidence: 87%

Properties of spontaneous depolarizations in circular smooth muscle cells of rabbit urethra

Hashitani

Helden

Suzuki

1996

British J Pharmacology

126

140

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“…CPA inhibits Ca-ATPase at the membrane of the sarcoplasmic reticulum (SR), thus depleting Ca 2ϩ from internal stores [79]. BAPTA chelates Ca 2ϩ , thereby reducing [Ca 2ϩ ] i [80]. As pointed out, caffeine has complex actions on smooth muscles and it also depletes Ca 2ϩ from internal stores [81].…”

Section: Properties Of Regenerative Potentials Generated By Bundles Omentioning

confidence: 99%

Cellular Mechanisms of Myogenic Activity in Gastric Smooth Muscle.

Suzuki

2000

JJP

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Many types of smooth muscle contract spontaneously, with each contraction being accompanied by a slow rhythmic oscillation of the membrane potential (slow wave), a discharge of spike potentials or both [1]. The spontaneous generation of a single spike or bursts of spikes is detected in smooth muscles of the urinary bladder, the uterus (longitudinal muscle layer), the prostate, the isolated longitudinal muscle of the intestine or the portal vein. Slow waves are observed in smooth muscle of the stomach, the circular layer of the intestine and uterus of many species, the renal pelvis, the urethra and the ureter. In several of these muscles, spike potentials are followed. These include the renal pelvis, ureter, uterus (circular muscle), lymphatic vessels and the urethra [2]. As many enteric nerves generate bursts of activity, the transmitters released from these nerves can modulate the activity of smooth muscles [3], and there is a possibility that smooth muscle activity could result indirectly as a consequence of neuronal activity. However, this is rarely the cause of muscle activity since many smooth muscles remain active after neuronal activity has been that ICC may also be the pacemaker cells responsible for gastric activity. However, isolated circular smooth muscle tissues spontaneously generate regenerative potentials, suggesting that there are at least two sites for the initiation of spontaneous activity in the stomach. Regenerative potentials persist in the presence of Ca-antagonists and are inhibited by agents which disrupt intracellular Ca 2ϩ homeostasis. Depolarization of the membrane elicits regenerative potentials after a long delay and the potentials have long refractory periods. This suggests that an unidentified 2nd messenger may be formed during the delay between membrane depolarization and the initiation of a regenerative potential. In gastric muscles of mutant mice which do not express inositol trisphosphate (InsP 3 ) receptors, spike potentials but not slow waves are generated, suggesting the possible involvement of InsP 3 in the initiation of spontaneous activity.

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“…With respect to mechanism of action, we have provided evidence earlier that the inhibition of spontaneous neurotransmitter release by adenosine occurs downstream of calcium entry at the frog neuromuscular junction [see, e.g., Silinsky, 1984;Hunt and Silinsky, 1993;Hunt et al, 1994]. While much confirmatory evidence has been obtained for this view at other synapses, there still is some controversy with respect to modulation of evoked neurotransmitter release [see Miller, 1998, for review].…”

Section: Presynaptic Inhibitory Effects Of Adenosine Analogsmentioning

confidence: 99%

Release and effects of ATP and its derivatives at cholinergic synapses

Silinsky

Searl

Redman

et al. 2001

Drug Development Research

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ATP is released from many central and peripheral terminals in a rapid, synchronous manner. It can act both as a neurotransmitter substance and as a neuromodulator in conjunction with a primary neurotransmitter. We begin this perspective by reviewing the evidence for the quantal release of ATP together with acetylcholine (ACh) from motor nerve endings. Next, we discuss the inhibitory effects of adenosine derivatives on presynaptic and postsynaptic membranes at cholinergic synapses. With regard to the presynaptic effects of adenosine, after hydrolysis to adenosine ATP is the mediator of skeletal neuromuscular depression at low frequencies of stimulation. The evidence confirming the suggestion that this inhibitory effect of adenosine at motor nerve endings is mediated downstream of calcium entry is presented. Finally, the data showing the mutually occlusive effects of ATP and ACh at cholinoceptive neurons are summarized and discussed. Drug Dev. Res. 52:22-33, 2001 OVERVIEWATP is released as a neurotransmitter proper in the peripheral and central nervous systems [Edwards et al., 1992;Silinsky and Gerzanich, 1993;Evans et al., 1992;Galligan and Bertrand, 1994; see Silinsky et al., 1998, for review]. ATP also is released together with neurotransmitter substances [Silinsky and Hubbard, 1973;Silinsky, 1975] and, once it is in the extracellular domain, can exert both presynaptic and postsynaptic actions on the release or effects of the neurotransmitter [for reviews see Silinsky et al., 1998;Burnstock and Williams, 2000]. This review focuses on the release of ATP and the effects of released ATP derivatives at presynaptic membranes strategically designed for the release of acetylcholine (ACh) and at postsynaptic membranes that possess nicotinic receptors for ACh. We begin by describing the detection of the release of ATP in response to discrete, temporally isolated nerve impulses from motor nerve endings together with the neurotransmitter ACh. We then review the evidence that this ATP release, after hydrolysis to adenosine, mediates presynaptic neuromuscular depression. Finally, we review the data showing the mutually occlusive postsynaptic effects of P2X ATP receptor activation and nicotinic receptor agonists. DETECTION OF ATP RELEASE FROM NERVE ENDINGS USING BIOCHEMICAL METHODSIn early studies of the co-release of ATP and ACh, the bathing fluid from stimulated preparations was removed and assayed for ATP by the luciferin-luciferase method [Silinsky and Hubbard, 1973;Silinsky, 1975]. These results suggested an intimate stoichiometry between the release of ATP and its hydrolysis products and the neurotransmitter ACh. ACh release was detected electrophysiologically by measuring evoked synaptic responses (end-plate potentials, or EPPs) and spontane-

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Reduction by intracellular calcium chelation of acetylcholine secretion without occluding the effects of adenosine at frog motor nerve endings

Cited by 13 publications

References 26 publications

Properties of spontaneous depolarizations in circular smooth muscle cells of rabbit urethra

Properties of spontaneous depolarizations in circular smooth muscle cells of rabbit urethra

Cellular Mechanisms of Myogenic Activity in Gastric Smooth Muscle.

Release and effects of ATP and its derivatives at cholinergic synapses

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