Substance P in the dorsal vagal complex inhibits medullary TRH-induced gastric acid secretion in rats.
Neurons that contain substance P (SP) and thyrotropin-releasing hormone (TRH) in medullary midline raphe nuclei project to the dorsal vagal complex (DVC). The modulatory role of SP on basal gastric acid secretion (GAS) and TRH on DVC-induced stimulation of GAS was studied in urethan-anesthetized rats. The stable SP agonist, DiMe-C7 ([pGlu5, MePhe8, MeGly9]SP5-11, 50 and 100 pmol), injected unilaterally into the DVC reduced the GAS response (47 +/- 12 mumol/60 min) to coinjected TRH analog, RX 77368 (25 pmol), by 53% and 85%, respectively, whereas DiMe-C7 (100 pmol) alone had no effect on basal and pentagastrin-stimulated GAS. DiMe-C7 (100 pmol/site) inhibited the GAS response to kainic acid injected into the raphe pallidus (Rpa) when it was injected bilaterally into the DVC but not the hypoglossal nuclei. The SP nourokinin-1-receptor antagonist, CP-96,345, injected bilaterally into the DVC (1 nmol/ site) increased basal GAS (33 +/- 8 mumol/90 min) and potentiated the GAS response to kainic acid injected into the Rpa by 40%. These results suggest that SP acts on neurokinin-1 receptors in the DVC to reduce medullary TRH-induced stimulation of GAS in rats.
Yang
H
H
CURE: Digestive Diseases Research Center, Department of Veterans Affairs Medical Center West Los Angeles, California, USA.
Taché
Y
Y
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002552:Cerebral Ventricles / Q000378:metabolism / Q000502:physiology*; D005744:Gastric Acid / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism / Q000502:physiology*; D008845:Microinjections; D010446:Peptide Fragments / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000378:metabolism / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology*
D001713:Biphenyl Compounds; D010446:Peptide Fragments; D013373:Substance P; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; C032720:substance P (5-11), pGlu(5)-MePhe(8)-MeGly(9)-; D007608:Kainic Acid; D011761:Pyrrolidonecarboxylic Acid; C066892:CP 96345