Effect of crotalfine on ion channels in sensory neurons

Resumo

The proposal presented here aims at the establishment of a partnership between the Butantan Institute in São Paulo and the Department of Physiology and Pathophysiology in Erlangen in order to study the molecular mechanisms involved in the analgesic action of crotalfina, a peptide isolated from the venom of the Brazilian rattlesnake Crotalus durissus terrificus. Studies carried out in Brazil characterised a potent and long-lasting analgesic effect of this peptide, which is why this compound is now in clinicai development. Crotalfine leads to indirect activation of kappa- and delta-opioid receptors and modulates intracellular enzymes such as PKC and MAP kinases. Furthermore, recent studies demonstrated that the mechanism of action of crotalfina leads to activation of nitric-oxide-cGMP and ATP-sensitive potassium channels. While these findings add to our knowledge, it is still unclear how crotalfina causes potent analgesia. Therefore we aimed to study potential interaction of the peptide with specific ion channels on nociceptive sensory neurons. Promissing studies carried out in the last months in the Department of Physiology and Pathophysiology demonstrated an interaction of crotalfine with the irritant receptor TRPA1. A collaboration between our research group would be valuable to continue these studies, which consist in identifying the molecular mechanism of analgesia by crotalphine and a common publication. In the future mutual visits will allow for knowledge transfer and exchange of research techniques between both laboratories. Scientists can receive on site training by qualified technicians and researchers which represents the basis for a later successfui implementation of novel research techniques in the Butantan Institute and for a long-term collaboration aiming at future collaborative projects and mutual supervision of PhD students in a cotutelle program. (AU)