Electrophysiological characterisation of tachykinin receptors in the rat nucleus of the solitary tract and dorsal motor nucleus of the vagus in vitro. 1997

K A Maubach, and R S Jones
Department of Pharmacology, University of Oxford, UK.

1. Recent studies have shown antagonists at the NK1 subtype of receptor for tachykinins are antiemetics and suggested that this may result from blockade of tachykinin-mediated synaptic transmission at a central site in the emetic reflex. 2. We have used intracellular recording in vitro to study the pharmacology of tachykinins in the nucleus of the solitary tract (NST) and dorsal motor nucleus of the vagus (DMNV). 3. Neurones in the NST were depolarized by substance P (SP), the presumed endogenous ligand for the NK1 receptor and these effects were mimicked by the NK1 agonists, SP-O-methylester (SPOMe), GR73632 and septide; however, SP was nearly an order of magnitude less potent than the latter two agonists. 4. In the DMNV, SP and NK1 receptor agonists evoked similar depolarising responses but SP appeared to be more potent than in the NST and was closer in potency to the other agonists. 5. NK1-receptor antagonists blocked responses to septide and GR73632 in the NST but had little effect on responses to SP and SPOMe. In contrast, in the DMNV the NK1-receptor antagonists blocked responses to septide and GR73632 but also reduced responses to SP and SPOMe. 6. Neurokinin A (NKA) was almost equipotent with septide and GR73632 in depolarizing both NST and DMNV neurones but these effects were not mimicked by a specific NK2-receptor agonist. Responses to NKA were unaffected by an NK2-receptor antagonist; however, the depolarizing effects of NKA were blocked by NK1-receptor antagonists. 7. Neurones in both DMNV and NST were unaffected by the endogenous NK3-receptor ligand, neurokinin B and by a specific agonist for this site, senktide. 8. The results with NK1 receptor agonists and antagonists suggest that the septide-sensitive NK1 site is involved in the excitation of both NST and DMNV neurones. The 'classical' NK1 receptor may play more of a role in the DMNV and a third unknown site may be responsible for the depolarizing response to SP in the NST. The effects of NKA are best interpreted as an action at the septide-sensitive NK1 site. This raises the possibility that anti-emetic action of the NK1 antagonists may be due to blockade of NKA transmission at the septide-sensitive site.

UI MeSH Term Description Entries
D008297 Male Males
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
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
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
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D017552 Solitary Nucleus GRAY MATTER located in the dorsomedial part of the MEDULLA OBLONGATA associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of AUTONOMIC NERVOUS SYSTEM regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of HOMEOSTASIS. The solitary nucleus is also notable for the large number of NEUROTRANSMITTERS which are found therein. Nucleus Solitarius,Nuclei Tractus Solitarii,Nucleus Tractus Solitarii,Nucleus of Solitary Tract,Nucleus of Tractus Solitarius,Nucleus of the Solitary Tract,Solitary Nuclear Complex,Solitary Tract Nucleus,Complex, Solitary Nuclear,Complices, Solitary Nuclear,Nuclear Complex, Solitary,Nuclear Complices, Solitary,Nuclei Tractus Solitarius,Nucleus Tractus Solitarius,Nucleus, Solitary,Nucleus, Solitary Tract,Solitarii, Nuclei Tractus,Solitarius Nucleus, Tractus,Solitarius, Nuclei Tractus,Solitary Nuclear Complices,Tractus Solitarii, Nuclei,Tractus Solitarius Nucleus,Tractus Solitarius, Nuclei
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018040 Receptors, Neurokinin-1 A class of cell surface receptors for TACHYKININS with a preference for SUBSTANCE P. Neurokinin-1 (NK-1) receptors have been cloned and are members of the G protein coupled receptor superfamily. They are found on many cell types including central and peripheral neurons, smooth muscle cells, acinar cells, endothelial cells, fibroblasts, and immune cells. NK-1 Receptors,Neurokinin-1 Receptors,Receptors, Substance P,SP-P Receptors,Substance P Receptors,NK-1 Receptor,Neurokinin-1 Receptor,Receptors, NK-1,Receptors, SP-P,SP-P Receptor,Substance P Receptor,Substance-P Receptor,Tachykinin Receptor 1,NK 1 Receptor,NK 1 Receptors,Neurokinin 1 Receptor,Neurokinin 1 Receptors,P Receptor, Substance,P Receptors, Substance,Receptor, NK-1,Receptor, Neurokinin-1,Receptor, SP-P,Receptor, Substance P,Receptor, Substance-P,Receptors, NK 1,Receptors, Neurokinin 1,Receptors, SP P,SP P Receptor,SP P Receptors
D064729 Neurokinin-1 Receptor Antagonists Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS. Neurokinin 1 Receptor Antagonist,Neurokinin-1 Receptor Antagonist,Neurokinin-1 Receptor Blocker,Neuroleukin-1 Receptor Blocker,Substance P Receptor Antagonist,Substance P Receptor Blocker,Tachykinin Receptor 1 Antagonist,Tachykinin Receptor 1 Blocker,Neurokinin-1 Receptor Blockers,Neuroleukin-1 Receptor Blockers,Substance P Receptor Antagonists,Substance P Receptor Blockers,Tachykinin Receptor 1 Antagonists,Tachykinin Receptor 1 Blockers,Antagonist, Neurokinin-1 Receptor,Antagonists, Neurokinin-1 Receptor,Blocker, Neurokinin-1 Receptor,Blocker, Neuroleukin-1 Receptor,Blockers, Neurokinin-1 Receptor,Blockers, Neuroleukin-1 Receptor,Neurokinin 1 Receptor Antagonists,Neurokinin 1 Receptor Blocker,Neurokinin 1 Receptor Blockers,Neuroleukin 1 Receptor Blocker,Neuroleukin 1 Receptor Blockers,Receptor Antagonist, Neurokinin-1,Receptor Antagonists, Neurokinin-1,Receptor Blocker, Neurokinin-1,Receptor Blocker, Neuroleukin-1,Receptor Blockers, Neurokinin-1,Receptor Blockers, Neuroleukin-1
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

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