Repeated delta1-opioid receptor stimulation reduces delta2-opioid receptor responses in the SA node
| Autor: | Matthew A. Barlow, Shekhar H. Deo, S. Johnson-Davis, James L. Caffrey, Darice Yoshishige |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Bradycardia
Male medicine.medical_specialty Physiology medicine.drug_class Enkephalin Methionine Microdialysis Narcotic Antagonists Stimulation Benzylidene Compounds Naltrexone Dogs Opioid receptor Physiology (medical) Internal medicine Receptors Opioid delta Heart rate Medicine Animals Receptor Sinoatrial Node Analgesics Dose-Response Relationship Drug business.industry Sinoatrial node Vagus Nerve Stimulation Chemical Vagus nerve Analgesics Opioid Endocrinology medicine.anatomical_structure Quinolines Female medicine.symptom Cardiology and Cardiovascular Medicine business Oligopeptides medicine.drug |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 291(5) |
| ISSN: | 0363-6135 |
| Popis: | Ultra-low-dose methionine-enkephalin-arginine-phenylalanine improves vagal transmission (vagotonic) and decreases heart rate via δ1-opioid receptors within the sinoatrial (SA) node. Higher doses activate δ2-opioid receptors, interrupt vagal transmission (vagolytic), and reduce the bradycardia. Preconditioning-like occlusion of the nodal artery produced a vagotonic response that was reversed by the δ1-antagonist 7-benzylidenaltrexone (BNTX). The following study tested the hypothesis that extended δ1-opioid receptor stimulation reduces subsequent δ2-receptor responses. The δ2-agonist deltorphin II was introduced in the SA node by microdialysis to evaluate δ2responses before and after infusion of the δ1-agonist TAN-67. TAN-67 reduced the vagolytic effect of deltorphin by two-thirds. When the δ1-antagonist BNTX was combined with TAN-67, the deltorphin response was preserved, suggesting that attrition of the prior response was mediated by δ1activity. When TAN-67 was omitted in time control studies, some loss of δ2responses was apparent in the absence of the δ1treatment. This loss was also eliminated by BNTX, suggesting that the attenuation of the response after deltorphin alone was also the result of δ1activity. Additional studies tested TAN-67 alone in the absence of prior deltorphin. When time controls were conducted without the initial deltorphin treatment, a robust vagolytic response was observed. When TAN-67 preceded the delayed deltorphin, the vagolytic response was eroded, indicating an independent effect of TAN-67. BNTX infused afterward was unable to restore the δ2response. These data support the conclusion that the loss of the δ2response resulted from reduced δ2activity mediated by continued δ1-receptor stimulation and not the arithmetic consequence of increased competition from that same δ1receptor. |
| Databáze: | OpenAIRE |
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