350 rub
Journal Technologies of Living Systems №7 for 2009 г.
Article in number:
DEFENSIN HNP-1 MODULATES THE RESPONSE OF SMALL INTESTINE IN-TRINSIC PRIMARY AFFERENT NEURONS TO MEDIATORS
Keywords: intrinsic primary afferent neurons (IPAN) small intestine duodenum acetylcoline serotonin (5-hydroxytryptamine) interleukin-1β histamine defensin HNP-1 protein kinase-C (PKC)
Authors:
Yu.A. Tolkunov
Abstract:
In our work we aimed to study intrinsic primary afferent neurons (iPAN-s) activity in the small intestine in response to mediators, and its modulation by the naturally occurring antibiotic of animal origin, defensin HNP-1. The experiments were conducted on the proximal fragments of guinea pig small intestine, using the specially developed method. This method includes the usage of intracellular glass capillary microelectrodes in isolated, or whole animal (guinea pig, anesthetized) small intestine preparations. We have shown that primary afferent neurons respond to the application of acetylcholine, 5-hydroxytryptamine, interleukine-1β, and histamine by generation of action potentials (AP-s) with mediator-specific characteristics. Defensin HNP-1 (1×1012 - 1×105 M) application to the bath solution did not produce considerable changes of iPAN-s resting membrane potential, while, at the same time, was able to suppress the generation of AP-s in these cells. This effect was reversible upon washout. Observed changes in neurons activity were mediated by the suppression of excitatory Na+ and Ca2+ currents. Defensin HNP-1 also disrupts K+ ions flow from the neuron. Intracellular application of defensin HNP-1 suppressed the generator potential and fast post-hyperpolarization of the APs generated by iPANs in response to histamine. We suggest that the intracellular action of defensin HNP-1 includes protein kinase-C inhibition. We conclude that defensin HNP-1 in the small intestinal wall acts to lower the primary afferent neurons response activity towards the main excitatory mediators.
Pages: 29-36
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