Lead Modulates Calcium Entry and Beta-Adrenoceptors Signaling to Produce Myometrial Relaxation in Rats

Nakade, Udayraj P.; Sharma, Abhıshek; Choudhury, Soumen; Yadav, Rajkumar Singh

doi:10.1007/s12011-016-0813-1

Cited by 7 publications

(3 citation statements)

References 17 publications

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“…Lead evoked concentration-dependent contractile effect on buffalo myometrium contrary to the inhibitory effect on rat myometrium (Nakade et al 2016). Compared to rat aortic rings (Valencia et al 2001), relatively much lower concentration of lead (0.1 mM Vs 3.1 mM) was required to induce maximal contractile effect on buffalo myometrium; thus suggesting higher sensitivity of buffalo myometrium to lead.…”

Section: Resultsmentioning

confidence: 74%

“…Spontaneous myometrial rhythmicity and uterotonics-induced myometrial contraction are regulated by calcium, and lead alters the dynamics of calcium either by interfering with the activity or metabolism of calcium or replacing it in physiological processes (Gupta and Fahim 2007). Lead exhibits extracellular calcium-independent vaso-reactive action in rat (Valencia et al 2001) while blocks Ca 2+ entry through VDCC and/or stimulates -adrenoceptors-adenylyl cyclase-cAMP pathways in rat myometrium (Nakade et al 2016). Calcium homeostasis mechanisms in myometrial smooth muscle differ from that in vascular beds, as myometrium exerts spontaneous rhythmicity with phasic and tonic contractions which too differ between cyclic and pregnant animals.…”

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confidence: 99%

“…Lead reportedly induces infertility, miscarriage, premature membrane rupture, pre-eclampsia, pregnancy hypertension and premature delivery (Flora et al 2011). Lead increases amplitude of spontaneous contraction with reduction in frequency induced by oxytocin and PGF 2 in bovine myometrium (Yildirim and Macun 2013), and produces inhibitory effect on rat myometrium (Nakade et al 2016). Lead evokes diverse actions (excitatory or inhibitory) on different tissues by modulating membrane receptors, downstream signaling molecules, calcium signaling or neurotransmitter release (Hore et al 2013, Nakade et al 2016.…”

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confidence: 99%

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Calcium-dependent and calcium-mimicking pathways regulate lead-induced myometrial contraction in water buffaloes

Nakade

Sharma

Choudhury

et al. 2017

Indian J of Anim Sci

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Lead produced dose-dependent contractile effect on buffalo myometrium and it was more marked on tonicity and amplitude while almost negligible on phasic contractions and frequency. In the presence of Ca2+-free Ringer Locke solution (RLS) and nifedipine, lead-induced uterotonic effect was significantly attenuated with decrease in Emax thus, suggesting major role of extracellular Ca2+ in uterotonic effect of lead and involvement of L-type Ca2+-channels in mediating this response. Direct excitatory effect of cyclopiazonic acid (CPA) on myometrium indicates possible Ca2+-influx via store operated calcium channels (SOCC). Lead failed to evoke any excitatory effect in the concurrent presence of nifedipine (1μM) and CPA (10μM), thus intracellular calcium seems to have negligible role in lead-induced myometrial contraction. In Ca2+-free high K+ (80 mM) depolarizing solution, lead-induced excitatory effect was attenuated by GF 109203X; which suggests permeation of lead through L-type Ca2+ channels to replace Ca2+ which directly activates protein kinase C (PKC) to produce excitatory effect. Thus lead seems to interact with calcium in buffalo myometrium in a dynamic fashion and exerts calcium-depending and calcium-mimicking effects; and therefore, lead is likely to have adverse effect on reproductive functions in buffaloes.

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Section: Resultsmentioning

confidence: 74%

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confidence: 99%

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confidence: 99%

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Calcium-dependent and calcium-mimicking pathways regulate lead-induced myometrial contraction in water buffaloes

Nakade

Sharma

Choudhury

et al. 2017

Indian J of Anim Sci

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Dose-Dependent Differential Effects of In Vivo Exposure of Cadmium on Myometrial Activity in Rats: Involvement of VDCC and Ca2+-Mimicking Pathways

Saroj

Nakade

Sharma

et al. 2017

Biol Trace Elem Res

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Present study was undertaken to study the effect of 28-days exposure of female adult rats to cadmium (Cd) in drinking water @ 3, 10 and 30 parts per million (ppm) on myometrial responsiveness to different spasmogens and unravel the possible mechanism of alterations in myometrial activity. Cadmium and Ca levels in blood and uterus were measured by atomic absorption spectroscopy while isometric tension in myometrial strips was measured using data acquisition system-based physiograph. Dose-dependent increase in levels of cadmium was observed in both blood and uterus while calcium was increased only in the uterus as compared to those in control. Significant increase in absolute tension and mean integral tension along with non-significant increase in frequency of myometrial contraction was observed in rats of Cd-treated groups. As compared to the control, cadmium decreased and increased the effects of calcium chloride, 80 mM KCl, histamine (0.1 μM) and oxytocin (10 IU/ml) in lower-dose (3 ppm) and higher-dose groups (10 and 30 ppm), respectively. Cadmium potentiated and inhibited the relaxant response to phenylephrine in myometrium of rats at lower-dose (3 ppm) and highest-dose (30 ppm) Cd-treated groups, respectively. Results of our study revealed that Cd accumulates in the myometrium of rats and alters its responsiveness to oxytocin, histamine, 80 mM KCl, calcium chloride and phenylephrine, and these effects are differentially mediated depending on levels of exposure possibly through voltage-dependent calcium channel (VDCC) and Ca-mimicking pathways.

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Calcium Channels, Rho-Kinase, Protein Kinase-C, and Phospholipase-C Pathways Mediate Mercury Chloride-Induced Myometrial Contractions in Rats

Koli¹,

Prakash²,

Choudhury³

et al. 2018

Biol Trace Elem Res

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Adverse effects of mercury on female reproduction are reported; however, its effect on myogenic activity of uterus and mechanism thereof is obscure. Present study was undertaken to unravel the mechanistic pathways of mercuric chloride (HgCl)-induced myometrial contraction in rats. Isometric tension in myometrial strips of rats following in vitro exposure to HgCl was recorded using data acquisition system-based physiograph. HgCl produced concentration-dependent (10 nM-100 μM) uterotonic effect which was significantly (p < 0.05) reduced in Ca-free solution and inhibited in the presence of nifedipine (1 μM), a L-type Ca channel blocker, thus suggesting the importance of extracellular Ca and its entry through L-type calcium channels in HgCl-induced myometrial contractions in rats. Cumulative concentration-response curve of HgCl was significantly (p < 0.05) shifted towards right in the presence of Y-27632 (10 μM), a Rho-kinase inhibitor, suggesting the involvement of Ca-sensitization pathway in mediating HgCl-induced myometrial contraction. HgCl-induced myometrial contraction was also significantly (p < 0.05) inhibited in the presence of methoctramine or para-fluoro-hexahydro-siladifenidol, a selective M and M receptor antagonists, respectively, which evidently suggest that mercury also interacts with M and M muscarinic receptors to produce myometrial contractions. U-73122 and GF-109203X, the respective inhibitors of PLC and PKC-dependent pathways, downstream to the receptor activation, also significantly (p < 0.05) attenuated the uterotonic effect of HgCl on rat uterus. Taken together, present study evidently reveals that HgCl interacts with muscarinic receptors and activates calcium signaling cascades involving calcium channels, Rho-kinase, protein kinase-C, and phospholipase-C pathways to exert uterotonic effect in rats. Graphical Abstract Graphical abstract depicting the mechanism of mercury-induced myometrial contraction in rats. M receptor: Muscarinic receptor; PIP2: phospho-inositol bisphosphate; PLC: phospholipase-C; DAG: diacyl glycerol; IP3: inositol triphosphate; IP3R: inositol triphosphate receptor; PKC; protein kinase-C; MLCP: myosin light chain phosphatise; MYPT: myosin phosphatase; SR: sarco-endoplasmic reticulum.

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Lead Modulates Calcium Entry and Beta-Adrenoceptors Signaling to Produce Myometrial Relaxation in Rats

Cited by 7 publications

References 17 publications

Calcium-dependent and calcium-mimicking pathways regulate lead-induced myometrial contraction in water buffaloes

Calcium-dependent and calcium-mimicking pathways regulate lead-induced myometrial contraction in water buffaloes

Dose-Dependent Differential Effects of In Vivo Exposure of Cadmium on Myometrial Activity in Rats: Involvement of VDCC and Ca2+-Mimicking Pathways

Calcium Channels, Rho-Kinase, Protein Kinase-C, and Phospholipase-C Pathways Mediate Mercury Chloride-Induced Myometrial Contractions in Rats

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