sr-144190 and vofopitant

Noxious challenge of the rat gastric mucosa by hydrochloric acid (HCl) is signalled via vagal afferent neurons to several brain nuclei in which tachykinins and tachykinin receptors are present. Therefore, we tested whether tachykinin receptor antagonists would modify the central transmission of input from the acid-threatened stomach. Neuronal excitation was visualized by in situ hybridization autoradiography (ISH) of c-fos messenger ribonucleic acid (mRNA) 45 min after intragastric (IG) administration of HCl (0.5 M; 10 ml/kg). This stimulus has previously been shown to cause neurons in the nucleus tractus solitarii (NTS), lateral parabrachial nucleus (LPB), paraventricular (Pa) nuclei, supraoptic (SO) nucleus, central amygdala (CeA), area postrema (AP), subfornical organ (SFO) and habenula (Hb) to express c-fos mRNA. Intraperitoneal (IP) pretreatment with the NK1 receptor antagonist GR-205,171 (3 mg/kg) attenuated the acid-induced transcription of c-fos mRNA in NTS and augmented it in SFO. The NK2 receptor antagonist SR-144,190 (0.1 mg/kg, IP) had no effect. Subcutaneous administration of the NK3 receptor antagonist SB-222,200 (20 mg/kg) reduced the c-fos mRNA response in AP and SFO and enhanced it in Hb. These data show that the transmission of input from the acid-threatened stomach in distinct brain nuclei involves tachykinins acting at NK1 and NK3 receptors, but not NK2 receptors.

Topics: Afferent Pathways; Animals; Antiemetics; Autoradiography; Brain; Female; Gastric Mucosa; Gene Expression; Hydrochloric Acid; In Situ Hybridization; Methylurea Compounds; Morpholines; Piperidines; Proto-Oncogene Proteins c-fos; Quinolines; Rats; Rats, Sprague-Dawley; Receptors, Tachykinin; RNA, Messenger; Stomach; Tetrazoles