The monosialosyl ganglioside GM-1 reduces the vagolytic efficacy of delta2-opioid receptor stimulation
| Autor: | Martin Farias, Darice Yoshishige, Shavsha Davis, Shekhar H. Deo, Matthew A. Barlow, James L. Caffrey |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Bradycardia
Male medicine.medical_specialty Microdialysis Enkephalin Physiology medicine.drug_class Enkephalin Methionine Narcotic Antagonists Stimulation G(M1) Ganglioside Benzylidene Compounds chemistry.chemical_compound Dogs Opioid receptor Physiology (medical) Internal medicine Receptors Opioid delta Heart rate medicine Animals Sinoatrial Node Ganglioside Dose-Response Relationship Drug business.industry Vagus Nerve Naltrexone Stimulation Chemical Analgesics Opioid Endocrinology chemistry Deltorphin Female medicine.symptom Cardiology and Cardiovascular Medicine business Oligopeptides |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 291(5) |
| ISSN: | 0363-6135 |
| Popis: | The cardiac enkephalin, methionine-enkephalin-arginine-phenylalanine (MEAP), alters vagally induced bradycardia when introduced by microdialysis into the sinoatrial (SA) node. The responses to MEAP are bimodal; lower doses enhance bradycardia and higher doses suppress bradycardia. The opposing vagotonic and vagolytic effects are mediated, respectively, by δ1and δ2phenotypes of the same receptor. Stimulation of the δ1receptor reduced the subsequent δ2responses. Experiments were conducted to test the hypothesis that the δ-receptor interactions were mediated by the monosialosyl ganglioside GM-1. When the mixed agonist MEAP was evaluated after nodal GM-1 treatment, δ1-mediated vagotonic responses were enhanced, and δ2-mediated vagolytic responses were reduced. Prior treatment with the δ1-selective antagonist 7-benzylidenaltrexone (BNTX) failed to prevent attrition of the δ2-vagolytic response or restore it when added afterward. Thus the GM-1-mediated attrition was not mediated by δ1receptors or increased competition from δ1-mediated vagotonic responses. When GM-1 was omitted, deltorphin produced a similar but less robust loss in the vagolytic response. In contrast, however, to GM-1, the deltorphin-mediated attrition was prevented by pretreatment with BNTX, indicating that the decline in response after deltorphin alone was mediated by δ1receptors and that GM-1 effectively bypassed the receptor. Whether deltorphin has intrinsic δ1activity or causes the release of an endogenous δ1-agonist is unclear. When both GM-1 and deltorphin were omitted, the subsequent vagolytic response was more intense. Thus GM-1, deltorphin, and time all interact to modify subsequent δ2-mediated vagolytic responses. The data support the hypothesis that δ1-receptor stimulation may reduce δ2-vagolytic responses by stimulating the GM-1 synthesis. |
| Databáze: | OpenAIRE |
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