We examined the intracellular mechanisms for the release of motilin in
a preparation of mucosal cells obtained from dog duodenum. Enzymatica
lly dispersed cells were separated by counterflow elutriation to enric
h motilin content. Postreceptor activation process was studied by comp
aring the release of motilin obtained with exogenous analogues or stim
ulants of the various intrecellular signal pathways. Dibutyryl cyclic
adenosine monosphate (10(-3) M) and forskolin (10(-5) M) induced a mod
erate response in motilin secretion. Phorbol ester beta-phorphol-12-my
ristate-13-acetate and phospholipase C were potent stimulants of motil
in release. Raising intracellular calcium concentration by calcium ion
ophore A23187 or increasing calcium content in the incubation milieu f
ailed to modify the secretion of motilin. Analogues of 8-bromoguanosin
e-3'5' cyclic monosphosphate were ineffective. Therefore, the motilin
cell was very sensitive to protein kinase C activators and appeared mo
derately responsive to a stimulation of the adenylate cyclase pathway.