A comparison of the effects of exogenous and endogenous prostaglandins on fast and slow contractions of field‐stimulated guinea‐pig vas deferens

Abstract

1 This study has compared the effects of exogenous and endogenous prostaglandins on the two phases of contraction of the guinea-pig vas deferens produced by electrical field stimulation. Prostaglandin E2 (PGE2), sulprostone and arachidonic acid dose-dependently and completely inhibited the first (fast) phase of contraction, with ICs5s of 2.6 nM, 0.65 nm and 2.2 14M, respectively.2 Following desensitization of the receptor for adenosine triphosphate (ATP) with a, f-methylene ATP, PGE2, sulprostone and arachidonic acid dose-dependently inhibited the second (slow) phase of contraction of the guinea-pig vas deferens produced by electrical field stimulation, but the inhibition was incomplete (up to only 30%). Indomethacin (2.8 uM) reduced the effect of arachidonic acid. On its own, indomethacin (0.3 to 6.0 pM) had no consistent effect although, on some tissues, a slight potentiation of the contractions was seen. 3 Cicaprost (a PGI2 analogue) at low concentrations (0.5 to 30 nM) potentiated the first phase of contraction but even at high concentrations, had no consistent effect on the second phase of contraction of the guinea-pig vas deferens produced by electrical field stimulation. 4 PGE2, sulprostone and cicaprost potentiated contractions of the guinea-pig vas deferens produced by exogenous ATP. PGE2-and sulprostone also potentiated contractions produced by exogenous noradrenaline, whereas cicaprost had no consistent effect on the response to noradrenaline. 5 These findings indicate that prostaglandins of the E-series inhibit the second phase of contraction as well as the first phase of contraction of the guinea-pig vas deferens produced by electrical field stimulation. However, the extent of the inhibition is much less for the second phase than for the first phase. The reasons for this differential action of PGE are not clear. 6 Cicaprost potentiates the first phase but not the second phase of contraction. Since cicaprost potentiates the contractions produced by exogenous ATP, but not by exogenous noradrenaline, by an action presumably on post-junctional IP receptors, the potentiating action of cicaprost on the first phase of contraction produced by electrical field stimulation would appear to be satisfactorily explained through the action of cicaprost on these post-junctional IP receptors. 7 Exogenous arachidonic acid is apparently converted predominantly to PGE2 by the vas deferens, since the action of arachidonic acid mimicked that of PGE2 and was reduced by indomethacin. However, there was little evidence thatufficient PGE2 is generated during a short period (15 s) of sympathetic nerve stimulation for it to have any-significant inhibitory effect on the size of the contractions produced.

The mechanisms of enhancement and inhibition of field stimulation responses of guinea‐pig vas deferens by prostacyclin analogues

“…Following the study of McKay and Poyser (1995) showing enhancement of ATP contractions by cicaprost, we decided to perform further experiments with conditions closer to their conditions of high ATP concentration (140–360 μ m ) in the absence of TTX. Tachyphylaxis to the high doses of ATP was minimized by first obtaining reproducible contractions to 5 μ m ATP challenges.…”

“…Since cicaprost did not affect direct contractile responses to exogenous NA, it was tentatively proposed that cicaprost activates presynaptic IP‐receptors to enhance transmitter release (Jones, 1993). However, McKay and Poyser (1995) subsequently found that cicaprost (1–100 n m ) enhanced the contractile action of ATP, but not that of NA, on the vas deferens. These observations are highly relevant since ATP is the transmitter mainly responsible for contractions of the vas deferens elicited by brief sympathetic nerve stimulation (Fedan et al , 1981; Sneddon & Westfall, 1984; Kirkpatrick & Burn‐stock, 1987).…”

Novel cyclooxygenase‐catalyzed bioactive prostaglandin F2α from physiology to new principles in inflammation

“…Gas-chromatography-mass spectrophotometry could also be used to determine 15-keto-dihydro-PGF 2a , but is rarely applied in large clinical or experimental studies due to its high cost and limited analyzing capability. Measurement of 15-keto-dihydro-PGF 2a in plasma or urine reflects the endogenous formation of primary PGF 2a during basal conditions or certain physiological processes that induce extensive PGF 2a biosynthesis and release into the circulation such as luteolysis, parturition, or induced abortion, [2][3][4][95][96][97] or during acute, sub-chronic, and chronic inflammation (experimental or clinical), 6,7,10,12 -15,94,98 or after an intravenous infusion of primary PGF 2a or their analogs, 3,99,100 and drug evaluation studies. 91,101-110…”

Neurogenic and non‐neurogenic responses in the urinary bladder of hibernating hamster

“…There is also some evidence that prostanoids have a facilitatory role on purinergic neurotransmission. Bradykinin, which induces contraction partially by a release of prostanoids, is able to increase significantly the ATP‐induced response in the rat bladder (Acevedo, 1990) and in guinea‐pig vas deferens an analogue of prostaglandin I 2 was able to potentiate the ATP‐induced responses (McKay & Poyser, 1995).…”