Myelination in the neonatal brain.

244 gallbladder. Like smooth mnscle, canalicular bile tlow is energy dependent. Agents tltat alter the antot, nt of ATI' in the cell sap have a similar effect on bile tlow rate. The rate of bile flow is modulated b)' a hormotte-receptor interaction attalogous to tire contraction-relaxation c)'cle of smooth muscle in which cAMI' and Ca + + are tire chief determinants. The same determinants are theoretically involved in the contraction attd relaxation of microfilaments in nonmuscle cell movement. To continue the analog)' between smooth ntttscle contraction and pericanalicular nticro-filament contraction, how could contraction of microfilaments generate the force that causes the flow of bile? Since tlte microfilaments are located arottnd the l)eripltery of the canalicu-lus? their contraction would narrow the lumen of tlte canaliculus and force the bile to ttow in tire direction of the bile ducts. It is likely tltat tire escape of bile from the canaliculus in tile direction of tire liver sinusoids is prevented b)' the tight junctions located at the margins of the canaliculus. Relaxation of the microfilaments wottld allow refilling of the catmlicultts with freshly secreted bile. Cyclic relaxation-fiilling attd contraction-flow wot, ld provide a forced pumplike meclmnisnl for bile flow. Alterations in any of tlte factors involved in this cyclic contraction relaxation meclmnisna wottld change the bile flow rate. Interference with any of the tnodulatittg factors involved in nonnmscle cell microfilament contraction and relaxation, suclt as hormone levels, receptor sensitivity, calcium flux, adenylate cyclase activity, phospltodies-terase activity, and tlte energy sttpply (ATI'), could lead to reduced bile flow and, hence, cholestasis. Just as ltormones regtdate smooth mttscle contraction and relaxation so do they regulate canalicular bile flow. Hormones tlmt regulate canalicular bile tlow include glucagon and lty-drocortisone. As is the case with smootlt muscle contraction and relaxation, bile acid independent bile flow is stintulated b)' cAMP and theo-ph)'llin. It is likely that glucagon stimulated bile tlow is mediated by the cAMI' system. Even bile salt ~stimulated bile flow could be dependent on a cAMI' initiated mechanism, since bile salts ltave been shown to increase the intracelhtlar level of cAMP in smootlt muscle. Bile salts, like theoplolline, probabl)" increase cAMP levels by inltibiting phospltodiesterase activity. Cholestasis cotfld result from an)' agent that interferes with the hormone receptor stim-nlated contraction of rite pericanalicular micro-filaments. For exantple, it is possible that tire acute cholestasis cattsed by cltlorpromazine cottld result front this postttlated ntechanism through its ability to …