EFFECT OF BROMOCRIPTINE ON PROSTACYCLIN RELEASE AND CYCLIC-NUCLEOTIDES ON RAT AORTIC AND UTERINE TISSUES

The effect of bromocriptine mesylate on cyclic nucleotides and PGI2 release by rat aortic and uterine tissues was investigated. Treatment of rats with bromocriptine (10 mg kg-1 I.P. daily for 14 days) increased PGI2 release by the thoracic aorta from 0.67 .+-. 0.02 to 1.4 .+-. 0.03 ng/mg wet tissue (P < 0.001; n = 6). This increase was antagonized by treatment with sulpiride (15 mg kg-1). Incubation of the arterial tissue with bromocriptine (50 .mu.g ml-1) in vitro also stimulated PGI2 release. Mepacrine (160 .mu.g ml-1) significantly decreased both basal and stimulated PGI2 release. Incubation of myometrial tissue from pregnant rats with bromocriptine (50 .mu.g ml-1) in vitro significantly decreased PGI2 release from 1.25 .+-. 0.07 to 0.60 .+-. 0.08 ng/mg wet tissue (P < 0.05, n = 6). It also elevated uterine cAMP from 40 .+-. 2 to 64 .+-. 3 pmols/100 mg wet tissue. Both effects were antagonized by sulpiride. Bromocriptine did not affect uterine cGMP or the cyclic nucleotides in the aorta. It is concluded that the increase in aortic PGI2 was mediated via activation of dopamine D-2 receptors that stimulate phospholipase A2 enzyme. The decrease in myometrial PGI2 release may be related to the increase in uterine cAMP resulting from activation of dopamine D-1 receptors. Previous studies suggested a role for PGI2 in implantation in the rat. The results suggest that the inhibitory effect on uterine PGI2 may underlie the reported inhibition of bromocriptine on implantation. On broad basis, the decrease in uterine PGI2 together with the reported luteolytic effect of bromocriptine point to a potential role for the compound in postcoital contraception.