Role of peripheral capsaicin-sensitive neurons and CGRP in central vagally mediated gastroprotective effect of TRH.
We investigated in conscious rats the role of capsaicin-sensitive neurons and alpha-calcitonin gene-related peptide (CGRP), the form preferentially expressed in capsaicin sensory neurons, in mediating intracisternal thyrotropin-releasing hormone (TRH) analogue-induced vagal muscarinic gastroprotection against ethanol lesions. The TRH analogue RX-77368 (1.5 ng ic) reduced by 78 and 66% gastric hemorrhagic lesions induced by intragastric intubation of 60 and 80% ethanol, respectively. alpha-CGRP (1 nmol/kg iv) inhibited by 88% gastric lesions induced by 60% ethanol, and this peptide action was blocked by the CGRP antagonist, CGRP-(8-37) (128 nmol/kg iv). The protective effect of RX-77368 against 60% ethanol was completely abolished by the CGRP monoclonal antibody 4901 (4.8 mg/kg iv), CGRP-(8-37) (128 nmol/kg iv), and capsaicin pretreatment (125 mg/kg). Gastric lesions induced by 60% ethanol were not altered by the CGRP antagonist or antibody alone but were enhanced by capsaicin pretreatment. These results suggest that the gastroprotection induced by intracisternal TRH analogue involves an interaction between central vagal efferent pathways and splanchnic sensory afferent terminals containing CGRP.
Kato
K
K
Center for Ulcer Research and Education/University of California, Los Angeles Digestive Disease Center 90073.
Yang
H
H
Taché
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D002211:Capsaicin / Q000633:toxicity*; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects / Q000294:innervation / Q000473:pathology*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*
D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D000431:Ethanol; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D011761:Pyrrolidonecarboxylic Acid