CCKA receptors mediate slow depolarizations in cultured mammalian sympathetic neurons

Knoper, S.R.; Meehan, Alan G.; Purnyn, S. L.; Coggan, Jay S.; Anthony, Todd L.; Kreulen, David L.

doi:10.1016/0014-2999(93)90729-2

Cited by 8 publications

(4 citation statements)

References 12 publications

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“…Vm = -59 mV. sympathetic ganglia ( Knoper et al 1993). Recently, a CCK,-mediated depolarization, involving an increased mixed cation conductance, has been reported in substantia nigra (Wu and Wang 1994).…”

Section: Discussionmentioning

confidence: 93%

“…By analogy to results at other sites, peptides can have multiple, prolonged actions mediated by a variety of receptor subtypes coupled to G proteins (e.g., Inoue et al 1988). Long-term peptidergic effects, such as the reductions in K+ conductances that occur in neurons of other structures (Boden and Hill 1988;Branchereau et al 1993;Knoper et al 1993), would be particularly influential in regulating activities within thalamocortical circuits. The possibility that CCK and other peptides might be released preferentially throughout AND D. A.…”

Section: Discussionmentioning

confidence: 99%

“…ated with a decreased RN that likely involve an increase in a mixed cation conductance (Dodd and Kelly 198 1;Jarvis et al 1992;Wu and Wang 1994). By contrast, in some neurons CCK-elicited depolarizations are associated with an increased RN resulting from decreases in a resting K+ conductance (Boden and Hill 1988;Branchereau et al 1993;Knoper et al 1993), an action similar to that in nRt where CCK suppresses a voltage-independent &. * conductance present at resting membrane potential.…”

Section: Discussionmentioning

confidence: 99%

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Cholecystokinin depolarizes rat thalamic reticular neurons by suppressing a K+ conductance

Cox

Huguenard²,

Prince³

1995

Journal of Neurophysiology

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1. The thalamic reticular nucleus (nRt) is innervated by cholecystokinin (CCK)-containing neurons and contains CCK binding sites. We used tight-seal, whole cell recording techniques with in vitro rat thalamic slices to investigate the action of CCK on neurons in nRt and ventrobasal thalamus (VB). 2. Brief applications of the CCK agonist cholecystokinin octapeptide (26-33) sulfated (CCK8S) evoked prolonged spike discharges in nRt neurons but had no direct effects on VB neuron activity. This selective excitatory action of CCK8S in nRt resulted from a long-lasting membrane depolarization (2-10 min) associated with an increased input resistance. Voltage-clamp recordings revealed that CCK8S reduced membrane conductance by 0.6-3.8 nS, which amounted to 5-54% of the resting conductance of these neurons. 3. The conductance blocked by CCK8S was linear over the range of -50 to -100 mV and reversed near the potassium equilibrium potential. Modifications of extracellular K+ concentration altered the reversal potential of the conductance as predicted by the Nernst equation. The K+ channel blocker Cs+, applied either intracellularly or combined intra- and extracellularly, blocked the response to CCK8S. 4. The CCK8S-induced depolarization persisted after suppression of synaptic transmission by either tetrodotoxin or a low-Ca2+, high-Mg2+ extracellular solution, indicating that the depolarization was primarily due to activation of postsynaptic CCK receptors and not mediated through the release of other neurotransmitters. 5. The selective CCKA antagonists L364,718 and Cam-1481 attenuated the CCK8S-induced depolarization, whereas the CCKB antagonist L365,260 had little or no effect on the depolarization. 6. Our findings indicate that CCK8S, acting via CCKA-type receptors, reduces a K+ leak current, resulting in a long-lasting membrane depolarization that can presumably modify the firing mode of nRt neurons. Through this effect, CCK actions in nRt may strongly influence thalamocortical function.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Cholecystokinin depolarizes rat thalamic reticular neurons by suppressing a K+ conductance

Cox

Huguenard²,

Prince³

1995

Journal of Neurophysiology

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“…Much of the vagal NANC inhibitory effect on the stomach is mediated by the release of nitric oxide onto gastric smooth muscle (1,10,24,37,41,44,45,68). Perfusion with CCK-8s induces an excitation in most neurons, including identified gastrointestinal-projecting DMV neurons (4,7,13,23,38,47,48,65,66,75,79). The excitatory effects of CCK-8s on vagal motoneurons imply that the gastroinhibition induced by brain stem apposition of CCK-8s is likely due to activation of the NANC vagal pathway rather than withdrawal of the vagal cholinergic pathway.…”

Section: Discussionmentioning

confidence: 99%

Effects of brain stem cholecystokinin-8s on gastric tone and esophageal-gastric reflex

Holmes¹,

Tong²,

Travagli³

2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Holmes GM, Tong M, Travagli RA. Effects of brain stem cholecystokinin-8s on gastric tone and esophageal-gastric reflex. Am J Physiol Gastrointest Liver Physiol 296: G621-G631, 2009. First published January 8, 2009 doi:10.1152/ajpgi.90567.2008.-The actions of cholecystokinin (CCK) on gastrointestinal functions occur mainly via paracrine effects on peripheral sensory vagal fibers, which engage vago-vagal brain stem circuits to convey effector responses back to the gastrointestinal tract. Recent evidence suggests, however, that CCK also affects brain stem structures directly. Many electrophysiological studies, including our own, have shown that brain stem vagal circuits are excited by sulfated CCK (CCK-8s) directly, and we have further demonstrated that CCK-8s induces a remarkable degree of plasticity in GABAergic brain stem synapses. In the present study, we used fasted, anesthetized Sprague-Dawley rats to investigate the effects of brain stem administration of CCK-8s on gastric tone before and after activation of the esophageal-gastric reflex. CCK-8s microinjected in the dorsal vagal complex (DVC) or applied on the floor of the fourth ventricle induced an immediate and transient decrease in gastric tone. Upon recovery of gastric tone to baseline values, the gastric relaxation induced by esophageal distension was attenuated or even reversed. The effects of CCK-8s were antagonized by vagotomy or fourth ventricular, but not intravenous, administration of the CCK-A antagonist lorglumide, suggesting a central, not peripheral, site of action. The gastric relaxation induced by DVC microinjection of CCK-8s was unaffected by pretreatment with systemic bethanecol but was completely blocked by N G -nitro-L-arginine methyl ester, suggesting a nitrergic mechanism of action. These data suggest that 1) brain stem application of CCK-8s induces a vagally mediated gastric relaxation; 2) the CCK-8s-induced gastric relaxation is mediated via activation of nonadrenergic, noncholinergic pathways; and 3) CCK-8s reverses the esophageal-gastric reflex transiently.vago-vagal reflexes; gastric reflexes ESOPHAGEAL DISTENSION has long been recognized to elicit a robust and reflexive gastric relaxation (21). Early models of gastrointestinal vago-vagal reflexes presented a framework to explain many of the features of the brain stem circuits devoted to gastric reflex control, whereby stimulation of sensory vagal afferent fibers activates second-order neurons of the nucleus tractus solitarii (NTS). Subsequently, these second-order neurons modulate the output of preganglionic neurons in the dorsal motor nucleus of the vagus (DMV) that, in turn, control gastric functions to complete the vago-vagal loop (reviewed in Ref. 72).The esophageal-gastric reflex (or receptive relaxation) decreases gastric tone and allows swallowed food to be transported to the stomach with a minimal increase in intragastric pressure. Neurophysiological studies by Jean first showed the association of neurons of the caudal brain stem with esophageal function (reviewed in Re...

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Characterization of cholecystokinin receptors in canine intestinal circular muscle

1995

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CCKA receptors mediate slow depolarizations in cultured mammalian sympathetic neurons

Cited by 8 publications

References 12 publications

Cholecystokinin depolarizes rat thalamic reticular neurons by suppressing a K+ conductance

Cholecystokinin depolarizes rat thalamic reticular neurons by suppressing a K+ conductance

Effects of brain stem cholecystokinin-8s on gastric tone and esophageal-gastric reflex

Characterization of cholecystokinin receptors in canine intestinal circular muscle

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