Biomaterial Database

Delta opioid receptors inhibit vagal bradycardia in the sinoatrial node. 2001

K E Jackson, and M Farias, and A Stanfill, and J L Caffrey

Department of Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center in Fort Worth, Fort Worth, Texas 76107, USA.

BACKGROUND Methionine-enkephalin-arginine-phenylalanine (MEAP) is an endogenous opiate derived from the C-terminal sequence of the larger precursor molecule proenkephalin. This heptapeptide is abundant in the myocardium and has significant vagolytic activity when infused systemically. MEAP interrupted vagal bradycardia when it was delivered directly into the sinoatrial node by local microdialysis. This study was conducted to determine the opioid receptor responsible for the vagolytic effect of MEAP. RESULTS Microdialysis probes were placed in the sinoatrial node of mongrel dogs and perfused at 5 microL/min. Increasing doses of MEAP were included in the nodal perfusate and approximately two thirds of the vagal bradycardia was inhibited with a maximal effect at 0.3 nmoles/microL and a half-maximal response near 0.1 nmoles/microL. When deltorphin II (a delta opioid receptor agonist) was infused into the sinoatrial node, more than 95% of the vagal bradycardia was eliminated at 0.3 nmoles/microL with the half-maximal response near 0.1 nmoles/microL, indicating that deltorphin II was more efficacious than MEAP. The maximal deltorphin II and MEAP effects were both similarly reversed by the paired infusion of increasing doses of the delta opiate receptor antagonist, naltrindole. Selected mu (endomorphin, super DALDA) and kappa (dynorphin, U50488) receptor agonists and mu (CTAP) and kappa (norBNI) receptor antagonists were completely ineffective in this system. CONCLUSIONS These data suggest that the vagolytic effect of MEAP involves the activation of delta opiate receptors within the sinoatrial node.

UI	MeSH Term	Description	Entries
D010446	Peptide Fragments	Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.	Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D011498	Protein Precursors		Precursors, Protein
D001919	Bradycardia	Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.	Bradyarrhythmia,Bradyarrhythmias,Bradycardias
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog
D004744	Enkephalin, Methionine	One of the endogenous pentapeptides with morphine-like activity. It differs from LEU-ENKEPHALIN by the amino acid METHIONINE in position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN.	Methionine Enkephalin,5-Methionine Enkephalin,Met(5)-Enkephalin,Met-Enkephalin,5 Methionine Enkephalin,Enkephalin, 5-Methionine,Met Enkephalin
D004745	Enkephalins	One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla.	Enkephalin
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012849	Sinoatrial Node	The small mass of modified cardiac muscle fibers located at the junction of the superior vena cava (VENA CAVA, SUPERIOR) and right atrium. Contraction impulses probably start in this node, spread over the atrium (HEART ATRIUM) and are then transmitted by the atrioventricular bundle (BUNDLE OF HIS) to the ventricle (HEART VENTRICLE).	Sinuatrial Node,Sinus Node,Sino-Atrial Node,Sinu-Atrial Node,Node, Sino-Atrial,Node, Sinoatrial,Node, Sinu-Atrial,Node, Sinuatrial,Node, Sinus,Nodes, Sino-Atrial,Nodes, Sinoatrial,Nodes, Sinu-Atrial,Nodes, Sinuatrial,Nodes, Sinus,Sino Atrial Node,Sino-Atrial Nodes,Sinoatrial Nodes,Sinu Atrial Node,Sinu-Atrial Nodes,Sinuatrial Nodes,Sinus Nodes
D013566	Sympathomimetics	Drugs that mimic the effects of stimulating postganglionic adrenergic sympathetic nerves. Included here are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters.	Amines, Sympathomimetic,Sympathomimetic,Sympathomimetic Agent,Sympathomimetic Drug,Sympathomimetic Agents,Sympathomimetic Drugs,Sympathomimetic Effect,Sympathomimetic Effects,Agent, Sympathomimetic,Agents, Sympathomimetic,Drug, Sympathomimetic,Drugs, Sympathomimetic,Effect, Sympathomimetic,Effects, Sympathomimetic,Sympathomimetic Amines
D014630	Vagus Nerve	The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx).	Cranial Nerve X,Pneumogastric Nerve,Tenth Cranial Nerve,Nerve X,Nervus Vagus,Cranial Nerve, Tenth,Cranial Nerves, Tenth,Nerve X, Cranial,Nerve Xs,Nerve, Pneumogastric,Nerve, Tenth Cranial,Nerve, Vagus,Nerves, Pneumogastric,Nerves, Tenth Cranial,Nerves, Vagus,Pneumogastric Nerves,Tenth Cranial Nerves,Vagus Nerves,Vagus, Nervus