Chronotropic Effect of Angiotensin II via Type 2 Receptors in Rat Brain Neurons
| Autor: | Philip Posner, Mingyan Zhu, Colin Sumners, Craig H. Gelband |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Chronotropic
medicine.medical_specialty Time Factors Pyridines Physiology Lipoxygenase Action Potentials Nerve Tissue Proteins Angiotensin II Type 2 Receptor Blockers Arachidonic Acids Tetrodotoxin Receptor Angiotensin Type 2 Synaptic Transmission Losartan Rats Sprague-Dawley Angiotensin Receptor Antagonists Internal medicine Okadaic Acid Phosphoprotein Phosphatases medicine Animals 12-Hydroxy-5 8 10 14-eicosatetraenoic Acid Lipoxygenase Inhibitors Enzyme Inhibitors Receptor Neurons Receptors Angiotensin Chemistry Angiotensin II General Neuroscience Cytarabine Imidazoles Brain Rat brain 5 8 11 14-Eicosatetraynoic Acid Rats Endocrinology Delayed rectifier Animals Newborn Signal Transduction |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1522-1598 0022-3077 |
| DOI: | 10.1152/jn.2001.85.5.2177 |
| Popis: | Previously, we determined that angiotensin II (Ang II) elicits an Ang II type 2 (AT2) receptor–mediated increase of neuronal delayed rectifier K+( I KV) current in neuronal cultures from newborn rat hypothalamus and brain stem. This requires generation of lipoxygenase (LO) metabolites of arachidonic acid (AA) and activation of serine/threonine phosphatase type 2A (PP-2A). Enhancement of I KV results in a decrease in net inward current during the action potential (AP) upstroke as well as shortening of the refractory period, which may lead to alterations in neuronal firing rate. Thus, in the present study, we used whole-cell current clamp recording methods to investigate the AT2 receptor–mediated effects of Ang II on the firing rate of cultured neurons from the hypothalamus and brain stem. At room temperature, these neurons exhibited spontaneous APs with an amplitude of 77.72 ± 2.7 mV ( n = 20) and they fired at a frequency of 0.8 ± 0.1 Hz ( n = 11). Most cells had a prolonged early after-depolarization that followed an initial fully developed AP. Superfusion of Ang II (100 nM) plus losartan (LOS, 1 μM) to block Ang II type 1 receptors elicited a significant chronotropic effect that was reversed by the AT2 receptor inhibitor PD 123,319 (1 μM). LOS alone had no effect on any of the parameters measured. The chronotropic effect of Ang II was reversed by the general LO inhibitor 5,8,11,14-eicosatetraynoic acid (10 μM) or by the selective PP-2A inhibitor okadaic acid (1 nM) and was mimicked by the 12-LO metabolite of AA 12-(S)-hydroxy-(5Z, 8Z, 10E, 14Z)-eicosatetraynoic acid. These data indicate that Ang II elicits an AT2 receptor–mediated increase in neuronal firing rate, an effect that involves generation of LO metabolites of AA and activation of PP-2A. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|