Potentiation of nerve-induced bladder contractions after calcium channel blockade

The potentiation of nerve-induced bladder contractions (NIC) by tetraethylammonium chloride (TEA), K+, or carbachol could result from a greater Ca2+ entry through Ca2+ channels in the muscle or from a greater release of transmitter by nerve terminals. Contractions of equal magnitude by the rat urinary bladder in vitro were initiated by carbachol, K+, or transmural stimulation of urinary bladder motor nerves at 1 Hz. Contractions elicited by K+ or carbachol were drastically reduced by verapamil (0.5 microM), but NICs were unaffected. Thus the role of Ca2+ channels in NICs seems uncertain. NICs are potentiated approximately 50% by K+ (15 mM), carbachol (0.5 microM), or 4-aminopyridine (0.2 mM) and over twofold by TEA (5 mM). Although verapamil (1–5 microM) reduced NICs in a dose-dependent relation, potentiation by each compound was the same. Thus Ca2+ channels probably play no role in potentiation. The resistance of the bladder to distention reflects its viscoelasticity and is Ca2+ sensitive. Because viscoelasticity was decreased by verapamil coincident with the reduction in NICs, both may result from lowered intracellular Ca2+ (Cai2+). However, because the potentiating compounds failed to restore bladder viscoelasticity, they probably did not elevate Cai2+. Therefore, in verapamil-treated preparations potentiation is most probably caused by an enhancement of transmitter release.

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Stimulation of β3-adrenoceptors relaxes rat urinary bladder smooth muscle via activation of the large-conductance Ca2+-activated K+ channels

AJP Cell Physiology ◽

10.1152/ajpcell.00001.2008 ◽

2008 ◽

Vol 295 (5) ◽

pp. C1344-C1353 ◽

Cited By ~ 65

Author(s):

Kiril L. Hristov ◽

Xiangli Cui ◽

Sean M. Brown ◽

Lei Liu ◽

Whitney F. Kellett ◽

...

Keyword(s):

Smooth Muscle ◽

Urinary Bladder ◽

Bk Channels ◽

Bk Channel ◽

Bladder Smooth Muscle ◽

Rat Urinary Bladder ◽

Urinary Bladder Smooth Muscle ◽

Brl 37344 ◽

Stimulation Of

We investigated the role of large-conductance Ca2+-activated K+ (BK) channels in β3-adrenoceptor (β3-AR)-induced relaxation in rat urinary bladder smooth muscle (UBSM). BRL 37344, a specific β3-AR agonist, inhibits spontaneous contractions of isolated UBSM strips. SR59230A, a specific β3-AR antagonist, and H89, a PKA inhibitor, reduced the inhibitory effect of BRL 37344. Iberiotoxin, a specific BK channel inhibitor, shifts the BRL 37344 concentration response curves for contraction amplitude, net muscle force, and tone to the right. Freshly dispersed UBSM cells and the perforated mode of the patch-clamp technique were used to determine further the role of β3-AR stimulation by BRL 37344 on BK channel activity. BRL 37344 increased spontaneous, transient, outward BK current (STOC) frequency by 46.0 ± 20.1%. In whole cell mode at a holding potential of Vh = 0 mV, the single BK channel amplitude was 5.17 ± 0.28 pA, whereas in the presence of BRL 37344, it was 5.55 ± 0.41 pA. The BK channel open probability was also unchanged. In the presence of ryanodine and nifedipine, the current-voltage relationship in response to depolarization steps in the presence and absence of BRL 37344 was identical. In current-clamp mode, BRL 37344 caused membrane potential hyperpolarization from −26.1 ± 2.1 mV (control) to −29.0 ± 2.2 mV. The BRL 37344-induced hyperpolarization was eliminated by application of iberiotoxin, tetraethylammonium or ryanodine. The data indicate that stimulation of β3-AR relaxes rat UBSM by increasing the BK channel STOC frequency, which causes membrane hyperpolarization and thus relaxation.

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Role of L- and N-type Ca2+ channels in muscarinic receptor-mediated facilitation of ACh and noradrenaline release in the rat urinary bladder.

The Journal of Physiology ◽

10.1113/jphysiol.1997.sp021957 ◽

1997 ◽

Vol 499 (3) ◽

pp. 645-654 ◽

Cited By ~ 22

Author(s):

G T Somogyi ◽

G V Zernova ◽

M Tanowitz ◽

W C de Groat

Keyword(s):

Urinary Bladder ◽

Muscarinic Receptor ◽

Noradrenaline Release ◽

Rat Urinary Bladder ◽

Ca2 Channels

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Impairment and restoration of rat urinary bladder responsiveness following distension

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1983.244.1.r106 ◽

1983 ◽

Vol 244 (1) ◽

pp. R106-R113 ◽

Cited By ~ 2

Author(s):

F. G. Carpenter

Keyword(s):

Diabetes Mellitus ◽

Urinary Bladder ◽

Transmitter Release ◽

Bladder Dysfunction ◽

Contractile Element ◽

Tetraethylammonium Chloride ◽

Rat Urinary Bladder ◽

Tension Development ◽

Resting Pressure

Micturition and bladder responsiveness in vitro were impaired in rats fed isotonic sucrose, afflicted with diabetes mellitus or diabetes insipidus. Their urinary output which was seven times control, initiated micturition responses at volumes three times control. Nerve-induced contractions by bladders from these rats developed substantially less pressure than control. Contractions elicited at 1 Hz by control and impaired bladders were potentiated equally by tetraethylammonium chloride (TEA) (5 mM) or by carbachol (2 X 10(-7) M). Contractions elicited at 20 Hz by normal bladders were not potentiated, those by impaired bladders were. TEA, by increasing transmitter release, and carbachol, by a postjunctional action, substantially reversed bladder dysfunction. Because control and impaired bladders were equally enhanced by TEA, prejunctional and contractile element (CE) activity at 1 Hz were probably unaffected by distension. However, postjunctional sensitivity was probably reduced. Impaired bladders, more compliant than controls, became less compliant after carbachol without elevating resting pressure. Whereas the action of carbachol to enhance bladder responsiveness did not involve tension development, there may have been cholinoceptor facilitation and shortening of CE.

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Vasorelaxant and Antihypertensive Effects of Mentha pulegium L. in Rats: An in vitro and in vivo Approach

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200909093908 ◽

2020 ◽

Vol 20 ◽

Author(s):

Mohammed Ajebli ◽

Mohamed Eddouks

Keyword(s):

Blood Pressure ◽

Acute Experiment ◽

Antihypertensive Activity ◽

Mentha Pulegium ◽

In Vitro Experiment ◽

Arterial Blood ◽

Dose Dependent ◽

Ca2 Channels

Aims and objective: The aim of the study was to investigate the effect of aqueous aerial part extract of Mentha pulegium L. (Pennyrile) (MPAE) on arterial pressure parameters in rats. Background: Mentha pulegium is a medicinal plant used to treat hypertension in Morocco. Material and methods: In the current study, MPAE was prepared and its antihypertensive activity was pharmacologically investigated. L-NAME-hypertensive and normotensive rats have received orally MPAE (180 and 300 mg/kg) during six hours for the acute experiment and during seven days for the sub-chronic treatment. Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were evaluated. While, in the in vitro experiment, isolated denuded and intact thoracic aortic rings were suspended in a tissue bath system and the tension changes were recorded. Results: A fall in blood pressure was observed in L-NAME-induced hypertensive treated with MPAE. The extract also produced a dose-dependent relaxation of aorta pre-contracted with NE and KCl. The study showed that the vasorelaxant ability of MPAE seems to be exerted through the blockage of extracellular Ca2+ entry. Conclusion: The results demonstrate that the extract of pennyrile exhibits antihypertensive activity. In addition, the effect may be, at least in part, due to dilation of blood vessels via blockage of Ca2+ channels.

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Amphetamine-Decreased Progesterone and Estradiol Release in Rat Granulosa Cells: The Regulatory Role of cAMP- and Ca2+-Mediated Signaling Pathways

Biomedicines ◽

10.3390/biomedicines9050493 ◽

2021 ◽

Vol 9 (5) ◽

pp. 493

Author(s):

Chung-Yu Chen ◽

Chien-Rung Chen ◽

Chiao-Nan Chen ◽

Paulus S. Wang ◽

Toby Mündel ◽

...

Keyword(s):

Granulosa Cells ◽

Prostaglandin F2α ◽

Inhibitory Effect ◽

Inhibitory Effects ◽

Steroidogenic Enzyme ◽

Estradiol Secretion ◽

Basal Release ◽

Ca2 Channels

The purpose of this study is to evaluate the amphetamine effects on progesterone and estradiol production in rat granulosa cells and the underlying cellular regulatory mechanisms. Freshly dispersed rat granulosa cells were cultured with various test drugs in the presence of amphetamine, and the estradiol/progesterone production and the cytosolic cAMP level were measured. Additionally, the cytosolic-free Ca2+ concentrations ([Ca2+]i) were measured to examine the role of Ca2+ influx in the presence of amphetamine. Amphetamine in vitro inhibited both basal and porcine follicle-stimulating hormone-stimulated estradiol/progesterone release, and amphetamine significantly decreased steroidogenic enzyme activities. Adding 8-Bromo-cAMP did not recover the inhibitory effects of amphetamine on progesterone and estradiol release. H89 significantly decreased progesterone and estradiol basal release but failed to enhance a further amphetamine inhibitory effect. Amphetamine was capable of further suppressing the release of estradiol release under the presence of nifedipine. Pretreatment with the amphetamine for 2 h decreased the basal [Ca2+]i and prostaglandin F2α-stimulated increase of [Ca2+]i. Amphetamine inhibits progesterone and estradiol secretion in rat granulosa cells through a mechanism involving decreased PKA-downstream steroidogenic enzyme activity and L-type Ca2+ channels. Our current findings show that it is necessary to study the possibility of amphetamine perturbing reproduction in females.

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Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity

International Journal of Molecular Sciences ◽

10.3390/ijms22094717 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4717

Author(s):

Jin-Young Lee ◽

Da-Ae Kim ◽

Eun-Young Kim ◽

Eun-Ju Chang ◽

So-Jeong Park ◽

...

Keyword(s):

Bone Resorption ◽

Bone Formation ◽

Map Kinases ◽

Osteoclast Differentiation ◽

Dependent Manner ◽

Dual Action ◽

Dose Dependent ◽

Resorptive Activity

Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.

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The Role of Interleukin-23 in the Early Development of Emphysema in HIV1+Smokers

Journal of Immunology Research ◽

10.1155/2016/3463104 ◽

2016 ◽

Vol 2016 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Igor Z. Barjaktarevic ◽

Ronald G. Crystal ◽

Robert J. Kaner

Keyword(s):

Tissue Destruction ◽

Epithelial Lining Fluid ◽

Protein Levels ◽

Knowing That ◽

Lung Epithelial ◽

Interleukin 23 ◽

Metalloproteinase 9 ◽

Stimulation Of

Rationale.Matrix metalloproteinase-9 (MMP-9) expression is upregulated in alveolar macrophages (AM) of HIV1+smokers who develop emphysema. Knowing that lung epithelial lining fluid (ELF) of HIV1+smokers contains increased levels of inflammatory cytokines compared to HIV1−smokers, we hypothesized that upregulation of lung cytokines in HIV1+smokers may be functionally related to increased MMP-9 expression.Methods.Cytokine arrays evaluated cytokine protein levels in ELF obtained from 5 groups of individuals: HIV1−healthy nonsmokers, HIV1−healthy smokers, HIV1−smokers with low diffusing capacity (DLCO), HIV1+nonsmokers, and HIV1+smokers with lowDLCO.Results. Increased levels of the Th17 related cytokine IL-23 were found in HIV1−smokers with lowDLCOand HIV1+smokers and nonsmokers. Relative IL-23 gene expression was increased in AM of HIV1+individuals, with greater expression in AM of HIV1+smokers with lowDLCO. Infection with HIV1in vitroinduced IL-23 expression in normal AM. IL-23 stimulation of AM/lymphocyte coculturesin vitroinduced upregulation of MMP-9. Lung T lymphocytes express receptor IL-23R and interact with AM in order to upregulate MMP-9.Conclusion. This mechanism may contribute to the increased tissue destruction in the lungs of HIV1+smokers and suggests that Th17 related inflammation may play a role.

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