Angiotensin II-induced ionic currents and signalling pathways in submandibular ganglion neurons.
Angiotensin II (Ang II) is one of the most important vasoconstrictive hormones but is also known to act as a neuromodulator and a neurotransmitter in the central and peripheral nervous system. The submandibular ganglion (SMG) neuron is a parasympathetic ganglion which receives inputs from preganglionic cholinergic neurons, and innervates the submandibular salivary gland to control saliva secretion. In this study, the effects of Ang II on SMG neurons were investigated using the whole-cell patch clamp technique. Membrane currents evoked by a ramp pulse from +50 to -100 mV (-150 mV/500 ms) were compared in both the absence and presence of Ang II. In eight neurons tested, 1 microM Ang II increased inward currents by 42.0+/-8.2%. The reversal potentials of the Ang II-induced current were 0.2+/-0.6 mV. These increase of inward currents by Ang II were antagonized by losartan, a selective antagonist of AT(1) receptors. Intracellular dialysis with 0.1mM guanosin 5'-O-(2-thiodiphosphate) (GDP-beta-S), a G-proteins blocker, and anti-G(q/11) antibody attenuated Ang II-induced ionic current. In addition, pretreatment of neurons with 10 microM staurosporine (stauro), a protein kinase C (PKC) inhibitor, 0.5 microM PMA, a PKC activator, and 10 microM KN-93, a Ca2+/calmodulin-dependent protein kinase II (CaM K II) inhibitor, attenuated Ang II-induced ionic current in SMG neurons. The data presented here demonstrated that Ang II-induced ionic current via G(q/11)-proteins involving both PKC and CaM K II pathways in SMG neurons.
Department of Physiology, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, 261-8502, Chiba, Japan.
Minako
M
Abe
Takayuki
T
Endoh
Takashi
T
Suzuki
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D019311:Staurosporine / Q000494:pharmacology; D013363:Submandibular Gland / Q000294:innervation*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007473:Ion Channels; D000804:Angiotensin II; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate