Src family kinase potentiates the activity of nicotinic acetylcholine receptor in rat autonomic ganglion innervating urinary bladder

Abstract

Src family kinases (SFKs), one of the tyrosine kinase groups, are primary regulators of signal transductions that control cellular functions such as cell proliferation, differentiation, survival, metabolism, and other important roles of the cell. One of the crucial functions of SFKs is to regulate the activities of various neuronal channels. In this study, we investigated the modulatory action of SFK on nicotinic acetylcholine receptors (nAChRs) expressed in rat major pelvic ganglion (MPG) neurons innervating the urinary bladder. PP1 and PP2 (5 μM), selective Src-kinase inhibitors, attenuated ACh-induced ionic currents and [Ca2+]i transients in MPG neurons, whereas PP3, an inactive analogue, had no effect. Blocking the tyrosine kinase activity of Src kinase by pp60 c-src inhibitory peptide also reduced the ACh-induced currents. Conversely, sodium orthovanadate (200 μM), a tyrosine phosphatase inhibitor, significantly augmented the ACh-induced currents. In the kinase assay, the activities of SFKs in MPG neurons were also inhibited by PP2, but not by PP3. These data suggests that SFKs may have a facilitative role on the synaptic transmission in rat pelvic autonomic ganglion.

Highlights ► The activities of α3β4 AChRs are positively regulated by Src kinase in MPG neurons innervating urinary bladder. ► Src kinase selective inhibitor reduced the protein tyrosine kinase activity in neurons innervating urinary bladder.

Abbreviations SFKs, Src kinases; PTK, protein tyrosine kinase; ACh, acetylcholine; MPG, major pelvic ganglion; nAChR, nicotinic acetylcholine receptor; [Ca2+]i, intracellular calcium ion concentration

Keywords Major pelvic ganglia; Nicotinic acetylcholine receptor; Src family kinase