Depolarization-stimulated cholecystokinin secretion is mediated by L-type calcium channels in STC-1 cells

1996 ◽  
Vol 270 (2) ◽  
pp. G287-G290 ◽  
Author(s):  
A. W. Mangel ◽  
L. Scott ◽  
R. A. Liddle
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Single Channel ◽  
Bay K 8644 ◽  
Ic50 Value ◽  
Single Channel Currents ◽  
Dose Dependent ◽  
Cck Release

To examine the role of calcium channels in depolarization-activated cholecystokinin (CCK) release, studies were performed in an intestinal CCK-secreting cell line, STC-1. Blockade of potassium channels with barium chloride (5 mM) increased the release of CCK by 374.6 +/- 46.6% of control levels. Barium-induced secretion was inhibited by the L-type calcium-channel blocker, nicardipine. Nicardipine (10(-9)-10(-5) M) produced a dose-dependent inhibition in barium-stimulated secretion with a half-maximal inhibition (IC50) value of 0.1 microM. A second L-type calcium-channel blocker, diltiazem (10(-9)-10(-4) M), also inhibited barium-induced CCK secretion with an IC50 value of 5.1 microM. By contrast, the T-type calcium-channel blocker, nickel chloride (10(-7)-10(-8) M), failed to significantly inhibit barium-induced CCK secretion. To further evaluate a role for L-type calcium channels in the secretion of CCK, the effects of the L-type calcium channel opener, BAY K 8644, were examined. BAY K 8644 (10(-8)-10(-4) M) produced a dose-dependent stimulation in CCK release with a mean effective concentration value of 0.2 microM. Recordings of single-channel currents from inside-out membrane patches showed activation of calcium channels by BAY K 8644 (1 microM), with a primary channel conductance of 26.0 +/- 1.2 pS. It is concluded that inhibition of potassium channel activity depolarizes the plasma membrane, thereby activating L-type, but not T-type, calcium channels. The corresponding influx of calcium serves to trigger secretion of CCK.

Influence of PLC and MLCK inhibitors and the role of L-calcium channels in the cat pulmonary vascular bed

1995 ◽  
Vol 269 (4) ◽  
pp. L507-L513 ◽  
Author(s):  
A. D. Kaye ◽  
B. D. Nossaman ◽  
I. N. Ibrahim ◽  
P. J. Kadowitz
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Kinase Inhibitor ◽  
Bay K 8644 ◽  
Ang Ii ◽  
Arterial Perfusion ◽  
Vascular Bed ◽  
Pressor Responses ◽  
Pulmonary Vascular Bed

The effects of U-73122, a phospholipase C (PLC) inhibitor, on pressor responses to angiotensin II (ANG II), norepinephrine (NE), serotonin (5-HT), BAY K 8644, and the thromboxane A2 (TxA2) mimic, U-46619, were studied in the pulmonary vascular bed of the intact-chest cat. Under conditions of constant lobar blood flow, injections of ANG II, NE, 5-HT, U-46619, and the calcium channel opener, BAY K 8644, into the lobar arterial perfusion circuit caused dose-related increases in lobar arterial pressure, which were reproducible with respect to time. Infusion of U-73122, a PLC inhibitor, into the perfused lobar artery at 10–100 micrograms/kg for 10 min significantly reduced responses to ANG II, serotonin, and NE; however, U-73122 did not alter responses to BAY K 8644 or to U-46619. In a separate series of animals, the effects of the myosin light chain kinase inhibitor, KT-5926, were investigated, and after infusion of KT-5926 into the perfused lobar artery at 1–2 micrograms/kg for 10 min, responses to ANG II, NE, 5-HT, BAY K 8644, and U-46619 were reduced significantly. In a final series of experiments, the effects of the L-type calcium channel blocker, nicardipine, were investigated, and infusion of the L-type calcium channel blocker into the perfused lobar artery at 0.5-1 microgram/kg for 10 min reduced responses to ANG II, BAY K 8644, and NE. However, nicardipine did not alter pressor responses to 5-HT or the TxA2 mimic, U-46619.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dihydropyridine calcium channel modulators on cardiac sodium channels

1988 ◽  
Vol 254 (1) ◽  
pp. H140-H147 ◽  
Author(s):  
A. Yatani ◽  
D. L. Kunze ◽  
A. M. Brown
Keyword(s):  
Calcium Channels ◽  
Sodium Channels ◽  
Single Channel ◽  
Bay K 8644 ◽  
Sodium Currents ◽  
Whole Cell ◽  
Blocking Effects ◽  
Voltage Dependent ◽  
Cardiac Sodium Channels ◽  
Single Channel Currents

To investigate whether cardiac sodium channels have dihydropyridine (DHP) receptors we studied the effects of the optically pure (greater than 95%) enantiomers of the DHPs PN200–110 and BAY-K 8644 and the racemic DHP nitrendipine (NTD). Whole cell and single-channel sodium currents were recorded from cultured ventricular cells of neonatal rats using the patch-clamp method. NTD reduced cardiac sodium currents in a voltage-dependent manner. Inhibitory effects were due to an increase in traces without activity. The unit conductance remained unchanged. At negative holding potentials, NTD transiently increased the probability of channel opening. Both (+) and (-) PN 200–110 blocked sodium channels, although the (-) isomer was about one order of magnitude less effective. The blocking effects were voltage dependent. (+) BAY-K 8644 had similar blocking effects. (-) BAY-K 8644 produced an increase in sodium currents due to an increased frequency of channel openings and a marked prolongation of open time without any significant change in unit conductance. The DHPs have effects on cardiac sodium whole cell and single-channel currents that appear identical to and are as stereospecific as their effects on cardiac calcium currents, although the concentrations required are larger. In contrast the inwardly rectifying potassium channel (IK1) is unaffected by these DHPs. We conclude that functionally equivalent DHP receptors are present in cardiac sodium and calcium channels but not potassium channels and take this as evidence of the homology between sodium and calcium channels.

scholarly journals Protective Actions of Cilnidipine: Dual L/N-Type Calcium Channel Blocker Against Hypertensive Renal Injury in Rats

2021 ◽  
Vol 14 (4) ◽  
pp. 1887-1893
Author(s):  
Gouher Banu Shaikh ◽  
Surekha Hippargi ◽  
Dewan S. A Majid ◽  
Kusal K Das
Keyword(s):  
Angiotensin Ii ◽  
Calcium Channels ◽  
Creatinine Clearance ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Renal Injury ◽  
Channel Blocker ◽  
Urinary Protein ◽  
Fourth Generation ◽  
Animal House

Background: Cilnidipine belongs to fourth generation dihydropyridine calcium channel blocker (CCB). It is a dual L & N-type CCB. L- type calcium channels are present on the vascular smooth muscle and N-type calcium channels are present on the presynaptic nerve terminals. Cilnidipine has a vasodilating effect, its action is slow and long lasting. Aim and objectives: Aim of present study was to demonstrate the beneficial effects of cilnidipine on the hypertensive renal injury rats. And our objectives is to assess renal injury parameters (Proteinuria, Creatinine clearance, Renal fibrosis/glomerulosclerosis) in response to chronic NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) treatment in the presence or absence of cilnidipine treatment. Material and methods: Male albino Wister rats were procured from institutional animal house, divided into 4 groups (n=6 in each group). Group1 treated with vehicle (control), group2 treated with cilnidipine, group3 treated with L-NAME, group4 treated with L-NAME & cilnidipine. 24 hour urinary protein and creatinine clearance were measured. Serum urea and creatinine levels are also measured. Urinary and serum Angiotensin II levels were measured. Histopathological examination of kidneys was performed. Results: Our results demonstrate that treatment with cilnidipine (group4) there is reduction in 24hr urinary protein, improvement in creatinine clearance. We observed there was renal glomerulosclerosis and tubular degeneration of kidney tubules in group3 rats and reduction of renal injury in group4 rats. We also found reduced urinary and serum Angiotensin II level in cilnidipine treated (group 4) rats. Conclusion: These findings indicated that cilnidipine act as renoprotective agent and reduces glomerular damage in L-NAME induced hypertensive rats.

ZC88, a novel N-type calcium channel blocker from 4-amino-piperidine derivatives state-dependent inhibits Cav2.2 calcium channels

2015 ◽  
Vol 1605 ◽  
pp. 12-21 ◽  
Author(s):  
Shuzhuo Zhang ◽  
Lujia Yang ◽  
Kang Zhang ◽  
Xiaoyan Liu ◽  
Weiwei Dai ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
State Dependent

Roles of High-Voltage–Activated Calcium Channel Subtypes in a Vertebrate Spinal Locomotor Network

2000 ◽  
Vol 84 (6) ◽  
pp. 2758-2766 ◽  
Author(s):  
A. Büschges ◽  
M. A. Wikström ◽  
S. Grillner ◽  
A. El Manira
Keyword(s):  
Calcium Channels ◽  
Synaptic Transmission ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
High Voltage ◽  
Channel Blocker ◽  
Motor Pattern ◽  
Burst Duration ◽  
Locomotor Rhythm ◽  
Spinal Cord Neurons

Lamprey spinal cord neurons possess N-, L-, and P/Q-type high-voltage–activated (HVA) calcium channels. We have analyzed the role of the different HVA calcium channels subtypes in the overall functioning of the spinal locomotor network by monitoring the influence of their specific agonists and antagonists on synaptic transmission and on N-methyl-d-aspartate (NMDA)–elicited fictive locomotion. The N-type calcium channel blocker ω-conotoxin GVIA (ω-CgTx) depressed synaptic transmission from excitatory and inhibitory interneurons. Blocking L-type and P/Q-type calcium channels with nimodipine and ω-agatoxin, respectively, did not affect synaptic transmission. Application of ω-CgTx initially decreased the frequency of the locomotor rhythm, increased the burst duration, and subsequently increased the coefficient of variation and disrupted the motor pattern. These effects were accompanied by a depression of the synaptic drive between neurons in the locomotor network. Blockade of L-type channels by nimodipine also decreased the frequency and increased the duration of the locomotor bursts. Conversely, potentiation of L-type channels increased the frequency of the locomotor activity and decreased the duration of the ventral root bursts. In contrast to blockade of N-type channels, blockade or potentiation of L-type calcium channels had no effect on the stability of the locomotor pattern. The P/Q-type calcium channel blocker ω-agatoxin IVA had little effect on the locomotor frequency or burst duration. The results indicate that rhythm generation in the spinal locomotor network of the lamprey relies on calcium influx through L-type and N-type calcium channels.

scholarly journals Agatoxin-IVA-Sensitive Calcium Channels Mediate the Presynaptic and Postsynaptic Nicotinic Activation of Cardiac Vagal Neurons

2001 ◽  
Vol 85 (1) ◽  
pp. 164-168 ◽  
Author(s):  
Jijiang Wang ◽  
Mustapha Irnaten ◽  
David Mendelowitz
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Patch Clamp Technique ◽  
Current Increase ◽  
Inward Current ◽  
Voltage Dependent Calcium Channel ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels

Whole cell currents and miniature glutamatergic synaptic events (minis) were recorded in vitro from cardiac vagal neurons in the nucleus ambiguus using the patch-clamp technique. We examined whether voltage-dependent calcium channels were involved in the nicotinic excitation of cardiac vagal neurons. Nicotine evoked an inward current, increase in mini amplitude, and increase in mini frequency in cardiac vagal neurons. These responses were inhibited by the nonselective voltage-dependent calcium channel blocker Cd (100 μM). The P-type voltage-dependent calcium channel blocker agatoxin IVA (100 nM) abolished the nicotine-evoked responses. Nimodipine (2 μM), an antagonist of L-type calcium channels, inhibited the increase in mini amplitude and frequency but did not block the ligand gated inward current. The N- and Q-type voltage-dependent calcium channel antagonists conotoxin GVIA (1 μM) and conotoxin MVIIC (5 μM) had no effect. We conclude that the presynaptic and postsynaptic facilitation of glutamatergic neurotransmission to cardiac vagal neurons by nicotine involves activation of agatoxin-IVA-sensitive and possibly L-type voltage-dependent calcium channels. The postsynaptic inward current elicited by nicotine is dependent on activation of agatoxin-IVA-sensitive voltage-dependent calcium channels.

Spinal Antinociceptive Action of an N-Type Voltage-dependent Calcium Channel Blocker and the Synergistic Interaction with Morphine

1996 ◽  
Vol 84 (3) ◽  
pp. 636-643 ◽  
Author(s):  
Keiichi Omote ◽  
Mikito Kawamata ◽  
Osamu Satoh ◽  
Hiroshi Iwasaki ◽  
Akiyoshi Namiki
Keyword(s):  
Spinal Cord ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Intrathecal Morphine ◽  
Tail Flick ◽  
Dependent Manner ◽  
Antinociceptive Effects ◽  
Voltage Dependent

Background Four different voltage-dependent calcium channels (L-, N-, T-, and P-types) are distinguished in the central nervous system. Both L- and N-type calcium channels have been implicated in the release of neurotransmitters from sensory neurons in the spinal cord. It has been demonstrated that intrathecal L-type calcium channel blockers, which alone do not exhibit any antinociceptive effects, potentiate the antinociceptive effect of intrathecal morphine. The current study was designed to investigate the antinociceptive effects of the intrathecally administered N-type calcium channel blocker, omega-conotoxin GVIA (omega-CgTx). The interaction between morphine and omega-CgTx at the level of the spinal cord also was examined. Methods In male Sprague-Dawley rats, lumbar intrathecal catheters were chronically implanted. Tail flick and mechanical paw pressure tests were used to assess thermal and mechanical nociceptive thresholds, respectively. Morphine, omega-CgTx, or a combination of morphine and omega-CgTx was administered intrathecally, and the nociceptive thresholds were determined. Isobolographic analyses were used to define the nature of the functional interactions between morphine and omega-CgTx. Results Intrathecal omega-CgTx produced antinociception in a dose- and time-dependent manner. Isobolographic analyses revealed that intrathecal omega-CgTx and morphine interacted synergistically in both nociceptive tests. Conclusions This study indicates the importance of the N-type calcium channel in the spinal cord on nociception and suggests the functional interaction between the N-type calcium channel blocker and opioid at the level of the spinal cord.

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