Pharmacology of tachykinin receptors on neurones in the ventral tegmental area of rat brain slices.
The pharmacology of tachykinin receptors within the ventral tegmental area of rat brain slices was studied using in vitro electrophysiological techniques. The selective tachykinin NK3 receptor agonist senktide (100 nM) increased the action potential firing rate from 1.9 to 3.9 Hz in 70% of spontaneously active cells tested (n = 27). Senktide was the most potent agonist tested with an EC50 of 4 nM. In contrast the NK1 receptor agonists substance P-O-methyl ester (100-300 nM) or GR 73632 (1 microM) were inactive at the concentrations tested. Responses to neurokinin B (EC50 = 32 nM) were not blocked by the tachykinin NK1 receptor antagonist CP 99,994 (1 microM) nor by the tachykinin NK2 receptor antagonist SR 48968 (300 nM). Similarly responses to the tachykinin NK2 receptor agonist beta-[Ala8]neurokinin A-(4-10) (EC50 = 427 nM) were not antagonised by the tachykinin NK2 receptor antagonist SR 48968 (300 nM) and thus were likely to be due to the activation of tachykinin NK3 receptors. These data demonstrate that NK3, and not NK1 or NK2 receptors, mediate the principal excitatory effects of exogenously applied tachykinin receptor agonists on dopamine neurones within the rat ventral tegmental area.
Seabrook
G R
GR
Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, Terlings Park, Harlow, Essex, UK.
Bowery
B J
BJ
Hill
R G
RG
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004594:Electrophysiology; D066298:In Vitro Techniques; D008839:Microelectrodes; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000187:drug effects; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects; D018039:Receptors, Tachykinin / Q000187:drug effects*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin; C054724:senktide; C064218:neurokinin A (4-10), beta-Ala(8)-; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B