Characterization of alpha-adrenoceptors in the late pregnant ovine uterine artery.

Ring segments of uterine artery from pregnant ewes within two weeks of term were used to study alpha-adrenoceptor-mediated contractions in vitro. The order of potency for the agonists giving the same maximum contractile effect was norepinephrine greater than epinephrine greater than phenylephrine much greater than methoxamine; whereas the maximum contraction to clonidine was about 42% of that to norepinephrine. Medetomidine caused inconsistent responses and B-HT 920 was ineffective. Phentolamine (10(-7) M) and prazosin (10(-7) M), significantly (P less than 0.005) inhibited epinephrine-induced contractions, whereas yohimbine (10(-7) M) was ineffective. Clonidine-induced contractions were blocked by prazosin (10(-8) and 10(-7) M) but were insensitive to yohimbine (10(-7) M). The dissociation constant (KB) of the competitive antagonist prazosin was determined with phenylephrine. The slope of the Schild plot was not significantly different from unity. The pA2 value of prazosin with phenylephrine was 9.1 +/- 0.2. The dissociation constant (KA) and the relationship between receptor occupancy and response for the full agonists norepinephrine and phenylephrine were analyzed using the irreversible antagonist dibenamine. The KA values of norepinephrine and phenylephrine were 1.5 +/- 0.4 x 10(-6) M and 2.5 +/- 0.8 x 10(-6) M, respectively. The occupancy response relationship was nearly linear and the half-maximal response to norepinephrine or phenylephrine was obtained with a 50% receptor occupancy. These results suggest that contraction to alpha-adrenoceptor agonists in the late pregnant ovine uterine artery is mediated primarily by alpha 1-adrenoceptors, and there appears to be no substantial alpha 1-adrenoceptor reserve in this tissue. The mediation of contraction via alpha 2-adrenoceptors is not prominent in this tissue.