Possible mechanisms of spasmolytic action of bile salts on the isolated guinea-pig gallbladder.

The spasmolytic action of bile salts on gallbladder smooth muscle could explain the alleged relief of biliary colic seen during bile acid therapy. The mechanisms of spasmolytic action of bile salts, ursodeoxycholate and deoxycholate were studied in the isolated gallbladder of guinea-pigs. The bile salts accelerated the 45Ca-efflux from the gallbladder with synchronous relaxation and inhibited the cellular 45Ca-uptake by the depolarized muscle preparation. Further, they sensitively inhibited CaCl2-induced contraction of the depolarized muscle. The tissue cyclic AMP content of the gallbladder was significantly elevated by the bile salts. Dibutyryl cyclic AMP mimicked the effects of bile salts on the Ca-efflux and the muscle relaxation, but showed no effect on the cellular Ca-uptake. From these results, it is suggested that the bile salts produce the relaxant action through accelerating Ca-efflux, which is probably coupled with the elevation of the cellular cyclic AMP level, and through suppressing the Ca-influx across the cell membrane.

Effects of perfusion flow rate, prostaglandin F2 alpha, phenylephrine, and serotonin on isolated, perfused brains of spontaneously hypertensive rats.

Effects of perfusion flow rate and three vasoconstrictors, phenylephrine, prostaglandin F2 alpha (PGF2 alpha) and serotonin, on isolated, perfused brain preparations of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY) were investigated. The basal perfusion pressure of the cerebral vascular beds at a flow rate of 2.5 ml/min was 48 +/- 3 mm Hg (n = 11) in SHR and 32 +/- 2 mm Hg (n = 12) in WKY (P less than 0.005). The perfusion pressures at all flow rates tested (2.5-6.5 ml/min) in SHR were significantly greater than those in WKY. Concentration-perfusion pressure curves for the vasoconstrictors showed that the brain vascular bed was much more reactive to serotonin compared with phenylephrine and PGF2 alpha. EC50 values (-logM) for serotonin in the perfused brains of SHR and WKY were 7.0 +/- 0.06 (n = 10) and 6.5 +/- 0.06 (n = 11), respectively (P less than 0.01). There were no differences in EC50 values for phenylephrine or PGF2 alpha between SHR and WKY. Exogenous serotonin and phenylephrine caused significantly greater maximal vasoconstrictor responses in SHR compared with WKY, while the pressor response to PGF2 alpha was very weak and no significant difference between SHR and WKY preparations was observed. These results indicate that cerebral vascular beds in SHR exhibit higher cerebrovascular resistance than those in WKY. and that reactivity and sensitivity to serotonin and reactivity to phenylephrine in SHR rats are enhanced to a greater extent compared to WKY.