Endomorphins potentiate acid-sensing ion channel currents and enhance the lactic acid-mediated increase in arterial blood pressure: effects amplified in hindlimb ischaemia
| Autor: | Joyce S. Kim, Henry L. Puhl, Julie K. Drobish, Victor Ruiz-Velasco, Mohamed Emad Farrag, Paul B. Herold, Marc P. Kaufman |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Mean arterial pressure Physiology Chemistry Long-term potentiation (+)-Naloxone Pharmacology Pertussis toxin Lactic acid 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Dorsal root ganglion Anesthesia medicine Reflex 030217 neurology & neurosurgery Acid-sensing ion channel |
| Zdroj: | The Journal of Physiology. 595:7167-7183 |
| ISSN: | 0022-3751 |
| DOI: | 10.1113/jp275058 |
| Popis: | Chronic muscle ischemia leads to accumulation of lactic acid and other inflammatory mediators with a subsequent drop in interstitial pH. Acid-sensing ion channels (ASICs), expressed in thin muscle afferents, sense the decrease in pH and evoke a pressor reflex known to increase mean arterial pressure. The naturally occurring endomorphins are also released by primary afferents under ischemic conditions. We examined whether high affinity mu opioid receptor (MOR) agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic acid-mediated pressor reflex. In rat dorsal root ganglion (DRG) neurons, exposure to E-2 in acidic solutions significantly potentiated ASIC currents when compared to acidic solutions alone. The potentiation was significantly greater in DRG neurons isolated from rats whose femoral arteries were ligated for 72 hr. Sustained ASIC current potentiation was also observed in neurons pretreated with pertussis toxin, an uncoupler of G proteins and MOR. The endomorphin-mediated potentiation was a result of a leftward shift of the activation curve to more basic pH values and a slight shift of the inactivation curve to more acidic pH values. Intra-arterial co-administration of lactic acid and E-2 led to a significantly greater pressor reflex than lactic acid alone in the presence of naloxone. Finally, E-2 effects were inhibited by pretreatment with the ASIC3 blocker (APETx2) and enhanced by pretreatment with the ASIC1a blocker psalmotoxin-1. These findings have uncovered a novel role of endomorphins by which the opioids can enhance the lactic acid-mediated reflex increase in arterial pressure that is MOR stimulation-independent and APETx2-sensitive. This article is protected by copyright. All rights reserved |
| Databáze: | OpenAIRE |
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