ELECTROPHYSIOLOGICAL CHARACTERIZATION OF TACHYKININ RECEPTORS IN THE RAT NUCLEUS OF THE SOLITARY TRACT AND DORSAL MOTOR NUCLEUS OF THE VAGUS IN-VITRO

1 Recent studies have shown antagonists at the NK1 subtype of receptor for tachykinins are antiemetics and suggested that this may result fr om blockade of tachykinin-mediated synaptic transmission at a central site in the emetic reflex. 2 We have used intracellular recording in v itro to study the pharmacology of tachykinins in the nucleus of the so litary tract (NST) and dorsal motor nucleus of the vagus (DMNV). 3 Neu rones in the NST were depolarized by substance P (SP), the presumed en dogenous ligand for the NK1 receptor and these effects were mimicked b y the NK1 agonists, SP-O-methylester (SPOMe), GR73632 and septide; how ever, SP was nearly an order of magnitude less potent than the latter two agonists. 4 In the DMNV, SP and NK1 receptor agonists evoked simil ar depolarising responses but SP appeared to be more potent than in th e NST and was closer in potency to the other agonists. 5 NK1-receptor antagonists blocked responses to septide and GR73632 in the NST but ha d 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 an d 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 N K1-receptor antagonists. 7 Neurones in both DMNV and NST were unaffect ed by the endogenous NK3-receptor ligand, neurokinin B and by a specif ic agonist for this site, senktide. 8 The results with NK1 receptor ag onists and antagonists suggest that the septide-sensitive NK1 site is involved in the excitation of both NST and DMNV neurones. The 'classic al' NK1 receptor may play more of a role in the DMNV and a third unkno wn 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 septi de-sensitive NK1 site. This raises the possibility that anti-emetic ac tion of the NK1 antagonists may be due to blockade of NKA transmission at the septide-sensitive site.