IMPAIRED RELEASE OF GALLBLADDER CALCITONIN-GENE-RELATED PEPTIDE IN HUMAN GALLSTONE DISEASE

Calcitonin gene-related peptide (CORP) is a neurotransmitter present i n the peripheral ends of sensory neurons of the gut and may modulate r eflexes of the enteric nervous system. We studied the release of CGRP in normal human gallbladders and in those containing gallstones to tes t the hypothesis that abnormalities of regulation of CORP release part icipate in gallstone formation. Human gallbladder strips were obtained from histologically normal organs removed during liver surgery (n = 8 ) or from patients operated upon for symptomatic cholelithiasis (n = 1 4). After removal of the mucosa, muscle strips were superfused with ox ygenated Kreb's buffer in an organ bath at 37 degrees C. Pharmacologic agents were added to the superfusate and samples were collected at a- min intervals for analysis. CGRP release was measured by a sensitive a nd specific radioimmunoassay and adjusted for tissue weight. In normal gallbladders, CORP release was stimulated sixfold over basal by capsa icin (10(-5) M) to 363 +/- 75 pg per gram of muscle per 2 min. This re lease was abolished by addition of somatostatin (SS) or the neural blo cker tetrodotoxin (TTX). Lesser degrees of CORP release were observed after nonspecific stimulation with K+ or phosphodiesterase inhibition with caffeine. In gallbladders with gallstones, capsaicin-induced CGRP release was 74 +/- 16 pg per gram of muscle per 2 min (20% of normal, P < 0.001). Release induced by caffeine and K+ was also inhibited com pared to normal gallbladder strips. Release of CORP from diseased stri ps was abolished by TTX and inhibited by SS to degrees similar to norm al tissue. CGRP release in normal human gallbladder muscle strips is i ncreased by the sensory neuron stimulant capsaicin, the nonspecific st imulant K+, and phosphodiesterase inhibition by caffeine. This release is abolished by blockade of axonal transmission with TTX and by SS. C ORP content and release from gallbladders containing gallstones are in hibited. Whether these observations have significance in gallstone for mation or are secondary processes remains to be seen. (C) 1995 academi c Press, Inc.