Modulation of gallbladder motility by intrinsic cholinergic neurons

The mechanical contraction and release of acetylcholine (ACh) were investigated by use of an isolated guinea pig gallbladder preparation subjected to transmural field stimulation. An increase in contraction amplitude was found to be related to the frequency (5-60 Hz) of applied stimulus. Treatment with tetrodotoxin and atropine prevented these electrically induced contractions. A simultaneous increase in the release of ACh was noted with electrical stimulation or depolarization by veratrine hydrochloride, and this increase was susceptible to blockade by tetrodotoxin. Neither contractions nor ACh release could be detected with stimulation at 0.1 Hz. When field stimulation was applied to contracted gallbladder induced by a supramaximal concentration of cholecystokinin octapeptide (CCK-8), a further increase in muscle tone was observed. The magnitude of this increase was frequency dependent. Although the onset of response to field transmural stimulation was relatively more rapid, the maximal response attained was only 70% of that elicited by CCK-8. When tissues were exposed to 2.2 X 10(-6) M CCK-8, the muscle contracted maximally but there was no increase in the efflux of [3H]ACh. These data provide a pharmacological characterization of the intrinsic gallbladder cholinergic neurons and demonstrate a possible role they may play in the control of gallbladder motility.