The nematode neuropeptide, AF2 (KHEYLRF‐NH2), increases voltage‐activated calcium currents in Ascaris suum muscle
Year: 2007
Type: article
Abstract: BACKGROUND AND PURPOSE: Resistance to all the classes of anti-nematodal drugs like the benzimidazoles, cholinergic agonists and avermectins, has now been recorded in parasites of animals and/or humans. The development of novel anthelmintics is an urgent and imperative need. Receptors of nematode neuropeptides have been suggested to be suitable target sites for novel anthelmintic drugs. EXPERIMENTAL APPROACH: To investigate the effect of AF2 on calcium-currents in Ascaris suum somatic muscle cells we employed the two-micropipette current-clamp and voltage-clamp techniques and a brief application of AF2. KEY RESULTS: Here we report the isolation of voltage-activated, transient, inward calcium currents. These currents are similar in characteristics to Caenorhabditis elegans UNC-2 type currents, non-L-type calcium currents. Following a 2-minute application of 1 microM AF2 , there was a significant long-lasting increase in the transient inward calcium current; AF2 increased the maximum current (from -84 nA to -158 nA) by shifting the threshold in the hyperpolarising direction (V (50) changed from -7.2 to -12.8 mV) and increasing the maximum conductance change from 1.91 to 2.94 microS. CONCLUSION AND IMPLICATIONS: These studies demonstrate a mechanism by which AF2 increased the excitability of the neuromuscular system by modulating calcium currents in nematodes. A selective small molecule agonist of the AF2 receptor is predicted to increase the contraction and act synergistically with cholinergic anthelmintics and could counter resistance to these compounds.
Source: British Journal of Pharmacology
Authors: S Verma, A P Robertson, R J Martin
Institution: Iowa State University
Language: English
Subfield: Small Animals
Field: Veterinary
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2082464247