The experiments outlined in this proposal are designed: (1) to test the hypothesis that pregnancy is associated with a reduction in the motility of the gastric antrum and gallbladder; (2) to determine whether the reduced motility can be attributed to the increased serum levels of 17Beta-extradiol and progesterone which occur during pregnancy; and (3) to investigate by what mechanisms pregnancy and the steroid hormaones affect the contractility of the tissues. The in vivo and in votro contractile responses of the antrum and gallbladder to known agonists will be evaluated in pregnant and hormone pretreated (individually and in combination) animals and the results compared with data obtained from control animals. The pretreatment schedule will produce serum levels of the hormones comparable to those measured during pregnancy. The basis for the proposed inhibitory effects will be investigated two ways. First, gastric antrum smooth muscle from control, pregnant, and hormone pretreated groups will be examined for differences in resting membrane potential, action potential waveform characteristics, and passive membrane properties using standard intracellular recording techniques. Second, gallbladder tissue from each of the groups will be compared with respect to their total intracellular calcium concentration and calcium influx in response to known agonists. the data obtained from this proposal should enhance our understanding of the alterations in gastrointestinal smooth muscle function which occur during pregnancy. In addition, the data will contribute to our understanding of the basic electrophysiology of the gastric antrum and the role that external calcium plays in regulating gallbladder contraction.
