Health Effects of Penitrem A – Gastrointestinal Issues

 

 

This page lists medical journal articles discussing the association between cardiovascular 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.

 

Linley J, Loganathan A, Kopanati S, Sandle GI, Hunter M. Evidence that two distinct crypt cell types secrete chloride and potassium in human colon. Gut. 2014 Mar;63(3):472-9. PMID: 23740188

Human colon may secrete substantial amounts of water secondary to chloride (Cl(-)) and/or potassium (K(+)) secretion in a variety of diarrhoeal diseases. Ion secretion occurs via Cl(-) and K(+) channels, which are generally assumed to be co-located in the colonocyte apical membrane, although their exact cellular sites remain unclear. Two types of crypt cells were identified. One (73% of cells) had whole-cell currents dominated by intermediate conductance (IK) K(+) channels under resting conditions, which developed large CFTR-mediated currents in response to increasing intracellular cAMP. The other (27% of cells) had resting currents dominated by BK channels inhibited by the BK channel blocker penitrem A, but insensitive to both forskolin and the IK channel blocker clotrimazole.

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Molinari E. J., Sullivan J. P., Wan Y., Brioni J. D., Gopalakrishnan M.. Characterization and modulation of [125I]iberiotoxin-D19Y/Y36F binding in the guinea-pig urinary bladder. European journal of pharmacology. 2000;388:155–161. PMID: 10666507

The radioligand binding characteristics of the Ca(2+)-activated K(+) channel ligand [125I]iberiotoxin-D19Y/Y36F were examined in guinea-pigurinary bladder membranes. Saturation analysis revealed a single class of high affinity binding sites in the bladder with a K(D) value of 45.6 pM and a B(max) value of 112 fmol/mg protein. Specific binding was displaced by unlabeled iberiotoxin and penitrem A, but not by blockers of other classes of K(+) channels.

Hollywood M. A., McCloskey K. D., McHale N. G., Thornbury K. D.. Characterization of outward K(+) currents in isolated smooth muscle cells from sheep urethra. American journal of physiology. Cell physiology. 2000;279. PMID: 10913009 

The perforated-patch technique was used to measure membrane currents in smooth muscle cells from sheep urethra. The transient current and a component of sustained current were blocked by iberiotoxin, penitrem A, and nifedipine but were unaffected by apamin or 4-aminopyridine, suggesting that they were mediated by large-conductance Ca(2+)-activated K(+) (BK) channels. When the BK current was blocked by exposure to penitrem A (100 nM) and Ca(2+)-free bath solution, there remained a voltage-sensitive K(+) current that was moderately sensitive to blockade with tetraethylammonium (TEA; half-maximal effective dose = 3.0 +/- 0.8 mM) but not 4-aminopyridine. Penitrem A (100 nM) increased the spike amplitude and plateau potential in slow waves evoked in single cells, whereas addition of TEA (10 mM) further increased the plateau potential and duration.

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McLeay L. M., Smith B. L., Munday-Finch S. C.. Tremorgenic mycotoxins paxilline, penitrem and lolitrem B, the non-tremorgenic 31-epilolitrem B and electromyographic activity of the reticulum and rumen of sheep. Research in veterinary science. 1999;66:119–127. PMID: 10208889 

The mycotoxic tremorgens penitrempaxilline and lolitrem B had profound effects on electromyographic (EMG) activity of smooth muscle of the reticulorumen in conscious sheep. Responses to penitrem revealed a greater sensitivity of smooth muscle than skeletal muscle. Effects included an inhibition of the vagally-dependent cyclical A and B sequences of contraction of the reticulorumen, an increase in their amplitude and an excitation of local intrinsic activity contributing to elevated baselines and the occurrence of chaotic activity of the reticulum. The excitatory local effects were partially blocked by atropine, indicating that stimulation of muscarinic cholinoceptors was involved.

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Hayes A. W., Phillips R. D., Wallace L. C.. Effect of penitrem A on mouse liver composition. Toxicon. 1977;15:293–300. PMID: 882992

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Farb R. M., Mego J. L., Hayes W.. Effect of mycotoxins on uptake and degradation of [125I] albumin in mouse liver and kidney lysosomes. Journal of toxicology and environmental health. 1976;1:985–990. PMID: 966326 

Treatment with citrinin, penitrem A, streigmatocystin, and zearalenone produced inhibition of proteolysis in kidney but not in liver phagolysosomes. All agents except penitrem A caused a decrease in uptake of labeled albumin into kidney cells.

 

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