W. J. Hall

The role of prostaglandins in cholinergic neurotransmission in the guinea pig

Prostaglandins have contrasting effects on neurotransmission at different cholinergic nerve endings. This is a report on the role of prostaglandins in a number of cholinergic preparations from the guinea pig. In the isolated ileum PGE1 (2 X 10(-10) to 5 X 10(-8) M) potentiated the response to electrical stimulation of the cholinergic nerves. PGE1 (10(-7 M) caused an increase in tone followed by a period of transient inhibition of twitch height. Responses to simulation of the ileum with drugs were not potentiated by PGE1. Responses of atropinized or plexus-free muscle to electrical stimulation were also not potentiated by PGE1. Acetylsalicylic acid (2.5 X 10(-4) M) diminished the twitch response and the output of acetylcholine from the ileum. Both effects were reversed by PGE1. Qualitatively similar observations were made on the trachea. It is concluded that prostaglandins facilitate acetylcholine release in the ileum and trachea. PGE1 diminished the effect of vagal stimulation on the heart rate. The response to stimulation of the phrenic nerve was not affected.

A study of perfused isolated dog saphenous vein

SummaryUSING constant flow perfusion with Tyrode solution, the response of an isolated canine saphenous vein segment to pervienous nerve stimulation and to drugs was studied.The preparation was arranged so that drugs could be applied either to the luminal surface or the adventitial surface. Pharmacological evidence suggests that the perivenous nerves were noradrenergic. A maximal constrictor response to electrical stimulation was obtained at a frequency of 20 Hz.Little change in response to electrical stimulation occurred over a temperature range from 36-20°C.The constrictor effect of noradrenaline applied to the intimal surface was greater than the effect of this amine applied adventitially. This difference persisted when the vein segment was cocainised.It is suggested that this difference in response cannot be explained solely on the basis of the noradrenergic uptake machanism.Isoprenaline relaxed the venous segment constricted by noradrenaline. This effect appeared to be due to the action of isoprenaline on beta receptors in the vein wall.Acetylcholine had a constrictor effect on this vein segment but angiotensin in the concentrations employed was without effect.

A bilateral antidiuresis to renal artery infusion of prostaglandin E1 in dogs treated with phenylbutazone.

1. In acute experiments, high levels of endogenous prostaglandins, provoked by operative stress, could obscure or alter the actions of infused prostaglandins on the kidney. For this reason we decided to compare the effects of infusing prostaglandin E1 into the renal artery of the dog before and after the administration of phenylbutazone, a prostaglandin synthetase inhibitor.

Seasonal changes in the sensitivity of frog skin to prostaglandin and the effect of external sodium and chloride on the response

SummaryIt has been reported that prostaglandin E1 stimulates sodium transport across isolated frog skin. This paper is primarily concerned with a seasonal change in the sensitivity of frog skin to prostaglandin E1 and F1∝. To determine prostaglandin action on sodium transport, the abdominal skin ofRana temporaria was mounted in an Ussing-type chamber and the shortcircuit current was recorded. In some experiments the skin potential and conductance were also measured.Arachidonic acid, a possible tissue precursor of prostaglandin also increases the short-circuit current. The prostaglandin action is independent of outside chloride and unchanged with 1/10 Ringer outside.The frog skin shows the same seasonal variation in sensitivity to prostaglandins as reported by others for anti-diuretic hormone. Cold season frogs gave large responses whereas summer frogs at ambient temperatures were quite refractory. Pyruvate can restore, in part, the ability of summer skins to respond to prostaglandin as for anti-diuretic hormone.It is concluded that the refractory nature of summer skins is due, in part, to a lack of a suitable energy source.

Dose and pH dependent effects of aspirin on Guinea-Pig ileum

SummaryDifferences in environmental pH and aspirin / indomethacin dosage could explain the conflict about the role of prostaglandins in neurotransmission in guinea-pig ileum in vitro. Neither spontaneous activity nor the responses to electrical stimuli (E.S.) were affected by changing the pH of the Tyrode solution. However, the dose of aspirin (2.4 x 10-4 M) which decreases the E.S. responses in Tyrode gassed with O2(pH 8.5), does not do so if the gas phase is carbogen (pH 7.4), but the response to histamine is increased. Switching the gas phase from oxygen to carbogen in the presence of a high dose of aspirin (4 x 10-3M) causes spontaneous contractures of the ileum which are abolished by reverting to oxygen aeration. Aspirin, in addition to its role as a prostaglandin synthetase inhibitor, has direct smooth muscle effects at pH 7.4. This can explain the divergence of opinion on the role of prostaglandins in neurotransmission in guinea-pig ileum.

The functional relationship of the longitudinal and circular muscle of the guinea-pig uterus and human fallopian tube

SummaryUterine horns from pregnant and non-pregnant guinea-pigs were suspended in Krebs solution and perfused at a constant rate of flow. Contractions of the circular muscle were recorded by monitoring the perfusion pressure. Longitudinal muscle activity was measured by isometric recording of longitudinal tension. This technique was also employed to study the isolated human fallopian tube.It was confirmed that contractions of the two muscle layers in the above tissues could be recorded by the technique employed without significant mechanical interaction. In the guinea-pig uterus the predominant form of spontaneous activity was the almost synchronous contractions of the two muscle layers, with changes in longitudinal tension slightly preceding the changes in perfusion pressure. In contrast, the two muscle layers of the human fallopian tube appear to operate independently. Furthermore the two muscle layers of the guinea-pig uterus reacted in a similar manner to a variety of stimuli. In the human fallopian tube prostaglandin E1 caused an increase in longitudinal tension, with inhibition of the rhythmic changes in perfusion pressure. The functional implications of these findings are discussed.

A pharmacological analysis of the response of dog anterior mesenteric vein to transmural electrical stimulation.

SummaryMONITORING the perfusing pressure, with constant flow perfusion, and isometric recording of longitudinal tension, the responses of the circular and longitudinal muscle in the wall of the dog anterior mesenteric vein to transmural electrical stimulation were recorded simultaneously. It was concluded from the results with tetrodotoxin and the local anaesthetic agents, cocaine and lignocaine, that the contractions were due to the excitation of nerves. The findings with alpha blocking agents, reserpine, guanethidine, hexamethonium and atropine, suggest that these nerves are post-ganglionic sympathetic noradrenergic fibres. This preparation may be a useful model for further studies on the innervation of venous smooth muscle.