Health Effects of Penitrem A – Muscle Issues

 

 

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

 

Hannigan KI, Large RJ, Bradley E, Hollywood MA, Sergeant GP, McHale NG, Thornbury KD. Effect of a novel BKCa opener on BKCa currents and contractility of the rabbit corpus cavernosum.  Am J Physiol Cell Physiol. 2016 Feb 15;310(4):C284-92. PMID: 26659726

Large-conductance Ca(2+)-activated K(+) (BKCa) channels are thought to play a key role in the regulation of corpus cavernosum smooth muscle (CCSM) excitability. The effect of the novel BKCa channel opener GoSlo-SR5-130 on electrical activity in isolated rabbit CCSM cells and mechanical activity in strips of rabbit CCSM was examined. Single-channel currents were observed in inside-out patches. These channels were sensitive to Ca(2+), blocked by penitrem A, and had a conductance of 291 ± 20 pS (n = 7). The research findings suggest that GoSlo-SR5-130 is an effective tool for the study of BKCa channels and that these channels can modulate CCSM activity and are possible targets for the treatment of erectile dysfunction.

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Kyle BD, Bradley E, Large R, Sergeant GP, McHale NG, Thornbury KD, Hollywood MA. Mechanisms underlying activation of transient BK current in rabbit urethral smooth muscle cells and its modulation by IP3-generating agonists. Am J Physiol Cell Physiol. 2013 Sep 15;305(6):C609-22. PMID: 23804200

We used the perforated patch-clamp technique at 37°C to investigate the mechanisms underlying the activation of a transient large-conductance K(+) (tBK) current in rabbit urethral smooth muscle cells. The tBK currents were blocked by iberiotoxin and penitrem A (300 and 100 nM, respectively) and were also inhibited when external Ca(2+) was removed or the CaV channel inhibitors nifedipine (10 μM) and Cd(2+) (100 μM) were applied. These data suggest that IP3-generating agonists can modulate the electrical activity of rabbit urethral smooth muscle cells and may contribute to the effects of neurotransmitters on urethral tone.

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Kyle B., Bradley E., Ohya S., et al. Contribution of Kv2.1 channels to the delayed rectifier current in freshly dispersed smooth muscle cells from rabbit urethra. American journal of physiology. Cell physiology. 2011;301. PMID: 21813710 

We have characterized the native voltage-dependent K(+) (K(v)) current in rabbit urethral smooth muscle cells (RUSMC) and compared its pharmacological and biophysical properties with K(v)2.1 and K(v)2.2 channels cloned from the rabbit urethra and stably expressed in human embryonic kidney (HEK)-293 cells (HEK(Kv2.1) and HEK(Kv2.2)). Cells were bathed in 100 nM Penitrem A (Pen A) to block large-conductance Ca(2+)-activated K(+) (BK) currents and depolarized to +40 mV for 500 ms to evoke K(v) currents. When stromatoxin was applied in the presence of Pen A, the AP duration was significantly prolonged. Similarly, stromatoxin increased the amplitude of spontaneous contractions threefold, but only after Pen A application. These data suggest that K(v)2.1 channels contribute significantly to the K(v) current in RUSMC.

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McGahon Mary K., Dawicki Jennine M., Scholfield C. Norman, McGeown J. Graham, Curtis Tim M.. A-type potassium current in retinal arteriolar smooth muscle cells. Investigative ophthalmology & visual science. 2005;46:3281–3287. PMID: 16123430 

By their control of membrane potential and intracellular free Ca(2+) ([Ca(2+)](i)), K(+) currents are pivotal in the regulation of arterial smooth muscle tone. The goal of the present study was to identify and characterize the A-type K(+) current in retinal microvascular smooth muscle (MVSM) and to examine its role in modulating membrane potential and cellular contractility. Inhibition of this current by 100 nM of the Ca(2+)-activated K(+) channel blocker, Penitrem A, revealed a rapidly inactivating K(+) current that resembled an A-type current. A-type current is the major voltage-dependent K(+) current in retinal MVSM and appears to play a physiological role in suppressing cell excitability and contractility.

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Morton Michael J., Hutchinson Katie, Mathieson Peter W., Witherden Ian R., Saleem Moin A., Hunter Malcolm. Human podocytes possess a stretch-sensitive, Ca2+- activated K+ channel: potential implications for the control of glomerular filtration. Journal of the American Society of Nephrology : JASN. 2004;15:2981–2987. PMID: 15579500 

Podocytes express many proteins characteristic of smooth muscle, such as actin and myosin. They also express receptors to several vasoactive agents, including acetylcholine and angiotensin II; these phenotypic properties suggest that podocytes are not static entities but may respond to physiologic stimuli. Channel activity was Ca(2+)- and voltage-dependent, being increased with an increase in Ca(2+) or depolarization, and inhibited by penitrem A. In whole-cell experiments, penitrem A inhibited outward currents to the same extent as tetra-ethyl ammonium (TEA) but did not affect the membrane potential.

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Wang L., Cross A. L., Allen K. L., Smith B. L., McLeay L. M.. Tremorgenic mycotoxins increase gastric smooth muscle activity of sheep reticulum and rumen in vitro. Research in veterinary science. 2003;74:93–100. PMID: 12507571

Responses to the tremorgenic mycotoxin penitrem A and others thought to be involved in ryegrass staggers, paxilline and lolitrem B (10(-10)-10(-6)M), were compared with those of control vehicle (0.1% DMSO). Penitrem A and paxilline enhanced spontaneously active preparations and the amplitude of contractions in response to electrical field stimulation (EFS). Responses to paxilline had a shorter latency than to penitrem A. Penitrem A, but not paxilline, increased responses to exogenous acetylcholine. Lolitrem B (10(-6)M) increased responses to EFS, but many responses were equivocal, possibly due to the lower solubility of lolitrem B in aqueous solutions compared to the other tremorgens. The results show that these mycotoxins have peripheral excitatory effects on the reticulorumen and it is suggested that such activity in vivo may reflexly affect centrally derived cyclical contractions.

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Smith B. L., McLeay L. M., Embling P. P.. Effect of the mycotoxins penitrem, paxilline and lolitrem B on the electromyographic activity of skeletal and gastrointestinal smooth muscle of sheep. Research in veterinary science. 1997;62:111–116. PMID: 9243707

The electromyographic (EMG) activity of skeletal muscle was investigated as a method of recording the tremorgenic activity of the mycotoxins penitrempaxilline and lolitrem B in sheep. EMG recordings were made concurrently from the abomasal antrum and duodenum to study the effects of these tremorgens on smooth muscle of the gut. Penitrem (2.2 to 7.5 micrograms kg-1) induced mild to moderate tremors within 15 to 20 minutes of injection which lasted for two to four hours. The best measure of tremor indicated by skeletal muscle EMG was recorded from the shoulder area. The responses of smooth muscle of the antrum and duodenum to the tremorgens were variable. They included inhibitory effects on the antrum but no stimulation. The tremorgens had inhibitory effects on the duodenum on some occasions but on others, phase III migrating myoelectric complex-like activity was stimulated.

 

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