Health Effects of Penitrem A – Reproductive Issues

 

 

This page lists medical journal articles discussing the association between reproductive issues and the mycotoxin known as penitrem A.

The Health Effects of Penitrem A page of the Paradigm Change site provides further information on the effects of this mycotoxin.

 

Sánchez-Carranza O, Torres-Rodríguez P, Darszon A, Treviño CL, López-González I. Pharmacology of hSlo3 channels and their contribution in the capacitation-associated hyperpolarization of human sperm. Biochem Biophys Res Commun. 2015 Oct 23;466(3):554-9. PMID: 26381170

Slo3 channels (mSlo3) primarily mediate mouse sperm K(+) currents and are essential for the capacitation-associated hyperpolarization (CAH). Whole-cell patch-clamp recordings showed that hSlo3 currents are inhibited: significantly by progesterone, Ba(2+) and quinidine; partially by Penitrem A and Charybdotoxin; and poorly by Iberiotoxin and Slotoxin.

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 Li Y, Lorca RA, Ma X, Rhodes A, England SK. BK channels regulate myometrial contraction by modulating nuclear translocation of NF-κB. Endocrinology. 2014 Aug;155(8):3112-22. PMID: 24914944

The large-conductance Ca(2+)-activated K(+) (BK) channel plays an essential role in maintaining uterine quiescence during pregnancy. Our objective was to determine whether the BK channel regulates uterine contraction, in part, by modulating NF-κB translocation into the nucleus. Our results showed that BK channel inhibitors paxilline and penitrem A induced translocation of NF-κB into the nucleus in both hTERT cells and uterine myocytes to a similar extent as LPS treatment, and LPS and paxilline similarly reduced BK channel currents. This study suggests that BK channels regulate myometrial contraction, in part, by modulating nuclear translocation of NF-κB.

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Ahn Hyung Seok S., Peña Ike, Kim Yong Chul C., Cheong Jae Hoon H.. 4-Chloro-7- trifluoromethyl-10H- benzo[4,5]furo[3,2-b]indole-1-carboxylic acid (TBIC), a putative BK (Ca) channel opener with uterine relaxant activities. Pharmacology. 2011;87:331–340. PMID: 21646818 

In the present study, we examined the uterine relaxant activity of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid(TBIC), a putative opener of the large conductance Ca(2+)-activated K(+) (BK(Ca)) channelTBIC concentration-dependently inhibited spontaneous uterine contractions. BK(Cachannel blockers penitrem A (100 nmol/l) and tetraethylammonium chloride (1 mmol/l) attenuated the inhibitory activities of TBIC (p < 0.001). These results demonstrate the uterine relaxant effects of TBIC in a mechanism of action largely referable to the potentiation of the BK(Ca) channels.

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Aaronson Philip Irving I., Sarwar Uzma, Gin Stephanie, et al. A role for voltage-gated, but not Ca2+-activated, K+ channels in regulating spontaneous contractile activity in myometrium from virgin and pregnant rats. British journal of pharmacology. 2006;147:815–824. PMID: 16415906 

The roles of voltage-gated (K(V)) and large conductance Ca2+-activated K+ (BK(Ca)) channels in regulating basal contractility in myometrial smooth muscle are unresolved. The aim of this study was to determine the effects of inhibition of these channels on spontaneous rhythmic contraction in myometrial strips from four groups of rats: nonpregnant and during early (day 7), mid- (day 14), and late (day 21) pregnancy. BK(Ca) channels were inhibited using iberiotoxin (1-100 nM), paxilline (1-10 microM) or penitrem A (1-500, or 3000 nM); K(V) channels were inhibited using tetraethylammonium (TEA; 1-10 mM) and/or 4-aminopyridine (4-AP; 1-5 mM). None of the selective BK(Ca) channel inhibitors significantly affected contractility in myometrial strips from either nonpregnant or pregnant animals. TEA and 4-AP still caused an increase in MIT following treatment with 3000 nM penitrem A or a combination of propranolol, phentolamine, atropine (all 1 microM) and capsaicin (10 microM) in myometrial strips from nonpregnant rats.

 

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