CENTRAL VAGAL ACTIVATION BY TRH INDUCES GASTRIC HYPEREMIA - ROLE OF CGRP IN CAPSAICIN-SENSITIVE AFFERENTS IN RATS

The role of calcitonin gene-related peptide (CGRP) in the vagal cholin ergic-mediated increase in gastric mucosal blood flow (GMBF) induced b y the stable thyrotropin-releasing hormone (TRH) analogue RX-77368 inj ected intracisternally (ic, 30 ng) was investigated in urethan-anesthe tized rats using the hydrogen gas clearance technique. alpha-CGRP (14 mu g.kg(-1).h(-1)) or bethanechol (150 mu g.kg(-1).h(-1)) infused clos e intra-arterially to the stomach or RX-77368 injected intracisternall y increased GMBF by 76, 102, and 131%, respectively, 30 min after admi nistration. The CGRP antagonist, human CGRP-(8-37) [hCGRP-(8-37)], inj ected intravenously (15 mu g/kg bolus and 3 mu g.kg(-1).h(-1)) inhibit ed by 100, 97, and 73% the gastric hyperemic response to alpha-CGRP, T RH analogue, and bethanechol, respectively, whereas the substance P an tagonist CP-96,345 (3 mg/kg iv) had no effect. In capsaicin-pretreated rats, hCGRP-(8-37) no longer blocked the increase in GMBF induced by intracisternal RX-77368. These results suggest that the gastric hypere mic response to central vagal activation induced by intracisternal TRH analogue at 30 ng is mediated by local effector function of capsaicin -sensitive afferent fibers releasing CGRP.