Bradykinin modulates the electrophysiology of cultured rat sensory neurons through a pertussis toxin-insensitive G protein
Abstract
Application of the nonapeptide bradykinin (BK) to rat sensory neurons in culture elicits two types of electrical responses in a subpopulation of the cells: (i) an excitatory inward cation current (I(BK)), and (ii) an inhibition of voltage-activated calcium currents (I(Ca)). Ion replacement experiments and current-voltage measurements indicate that I(BK) shows little selectivity for monovalent cations. We investigated the role of GTP-binding proteins in the BK signal transduction pathway. Internal dialysis of neurons with the inhibitory guanine nucleotide analogue, GDPbetaS, decreased the percentage of cells responding and the magnitude of the responses. This finding lead us to propose that a G protein is involved in this transduction pathway. We have attempted to identify the G protein subtype involved using pretreatment with the bacterial toxins pertussis toxin (PTX) and cholera toxin (CTX). PTX potentiated I(BK) slightly, but had no effect on the inhibition of I(Ca) by BK. In contrast, PTX pretreatment blocked the effects of norepinephrine and neuropeptide Y on I(Ca), confirming that the PTX was capable of interfering with appropriate G protein signaling in these neurons. Pretreatment with CTX had no effect on the BK-induced ...Continue Reading
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Multiple Inhibitory Mechanisms of Lidocaine on Bradykinin Receptor Activity in Model Sensory Neurons
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