ACTION OF PROSTAGLANDIN

E2

ON THE RELEASE OF

CATECHOLAMINES FROM THE CANINE ADRENAL GLAND AND ITS INTERACTION WITH ACETYLCHOLINE

K. YAMASHITA, M. MIENO, T. SHIMIZU

AND

ER. YAMASHITA

Department of Pathophysiology, Atomic Disease Institute, Nagasaki University School of Medicine, Nagasaki 852, Japan

(Received 29 November 1977) SUMMARY

The effect of prostaglandin E2 (PGE2) on the secretion of adrenaline and noradrenaline by the adrenal gland and the interaction between PGE2 and acetylcholine in the adrenal medulla were examined in anaesthetized dogs. In splanchnicotomized dogs, i.v. injection of PGE2 failed to induce any secretion of catecholamines from the adrenal gland, whereas administration of PGE2 into the lumboadrenal artery resulted in a slight, approximately dose-dependent increase in catecholamine secretion within 2 min of the injection. This effect of PGE2 was unaffected by i.v. administration of atropine. Intravenous administration of acetylcholine 1 min after the administration of PGE2 into the lumboadrenal artery of splanchnicotomized atropine-treated dogs had a markedly greater effect on adrenal catecholamine secretion; the resultant output was about twice that evoked by acetylcholine in the absence of PGE2. The effect was more than additive, since the response to acetylcholine was at least one order of magnitude greater than that to PGE2. This indicates that PGE2 and acetylcholine may act synergistically in the adrenal medulla. INTRODUCTION

early demonstration (Ramwell, Shaw, Douglas & Poisner, 1966) of the presence of prostaglandin Fla in the adrenal medulla and its release by acetylcholine suggested that prostaglandins may play an important part in the secretory activity of the adrenal medulla. However, the effects of administration of prostaglandins to various species are confusing, in that no effect, stimulatory effects and inhibitory effects have all been reported (Horton, 1963 ; Kayaalp & Türker, 1967; Boonyaviroj & Gutman, 1977). Moreover, there is no evidence that prostaglandins can play an interactive role in the catecholamine-releasing action of acetylcholine or splanchnic nerve stimulation (Kayaalp & Türker, 1967; Miele, 1969; Hedqvist, 1970) and it is therefore possible that they are not involved in the secretory mechanisms of the adrenal medulla. In order to investigate this problem further, the effects of prostaglandin E2 (PGE2) on the secretory activity of the dog adrenal medulla have been determined. First, the immediate effect of administration of PGE2 into the lumboadrenal artery on the secretion of adrenal catecholamines was examined and secondly, the possibility of any interaction occurring between PGE2 and acetylcholine was also studied.

An

MATERIALS AND METHODS

Prostaglandin E2 Roche, Basle) was

Materials from gift Nippon Upjohn Ltd (Tokyo). Acetylcholine (Hoffmann-La purchased from Nippon Roche Ltd (Tokyo) and atropine sulphate

was a

(E. Merck, Darmstadt) from Nakarai Chemicals Ltd (Osaka). Prostaglandin E2 was injected in 1 ml 0-3% ethanol-isotonic saline; acetylcholine and atropine were administered in 1 ml 0-9% saline. Experimental animals and procedures Adult mongrel dogs of both sexes weighing between 6-5 and 18-4 kg were used. The opera¬ tions and actual experiments were performed under pentobarbitone (Nembutal, Abbott Laboratories, North Chicago, U.S.A. ; 25 mg/kg, injected i.v.) anaesthesia. In each.dog, the left lumboadrenal vein was approached through a longitudinal incision in the left lumbar area and cannulated (Satake, Sugawara & Watanabe, 1927) ; simultaneously, the left lumboadrenal artery supplying the left adrenal gland was catheterized in a retrograde direction and the left splanchnic nerves were sectioned. Prostaglandin E2 In one experiment, PGE2 (1 or 10 µg/kg body weight) was injected into either the left saphenous vein or the left lumboadrenal artery and the controls received vehicle only; in a further experiment PGE2 (1 µg/kg body weight) was administered into the lumboadrenal artery 15 min after i.v. injection of atropine (1 mg/kg body weight). The period of injection was 30 s. Samples of adrenal venous blood were withdrawn into graduated conical test-tubes for periods of 2 min beginning 10 min before, immediately after and 5, 15 and 30 min after the start of the PGE2 injection. Since the cannulation technique used in the present study permitted the collection of total adrenal effluent blood, the flow rate (ml kg body weight-1 min-1) of adrenal venous blood was estimated from the body weight and the volume of blood collected in unit time.

Prostaglandin E2 and acetylcholine Acetylcholine (1 mg/kg body weight) was injected into the left saphenous vein of each dog over a period of 15 s. Fifty-nine minutes after this injection, PGE2 (1 µg/kg body weight) was injected into the left lumboadrenal artery over a period of 30 s and after a further 30 s, each dog received a second injection of acetylcholine. In these experiments, atropine (1 mg/kg body weight, a dose known not to affect the response of the adrenal medulla to acetylcholine : Yamashita, Mitamura, Inoue & Akimoto, 1958) was administered 15 min before each injection of acetylcholine to prevent an abrupt fall in blood pressure. Adrenal venous blood was collected 10 min before the injection of acetylcholine and also during two succes¬ sive 60 s periods after the start of each acetylcholine injection. Finally, the rates of secretion of adrenaline and noradrenaline induced by acetylcholine before and after the administration of PGE2 were compared. Analyses Each blood sample was centrifuged immediately under refrigeration and plasma (1 ml) was analysed for adrenaline and noradrenaline by the trihydroxyindole (THI) method of von Euler & Lishajko (1959). The sensitivities of this method for adrenaline and noradrenaline were 10 and 20 ng respectively (Yamashita, Mieno & Shimizu, 1976). The fluorescence of PGE2, acetylcholine and atropine was also checked by the THI method and negative results were obtained. The rate of secretion of hormone from one adrenal gland was expressed as µg kg body weight-1 min-1, calculated from the concentration of hormone in adrenal venous plasma ^g/ml) and the rate of flow of adrenal venous plasma (ml kg body weight-1 min-1). Statistical comparisons were made by Student's i-test; a probability of < 0-05 was accepted as

statistically significant.

RESULTS

Prostaglandin E2 of Intravenous injection PGE2 (10 µg/kg, five dogs) did not significantly alter the adrenal of catecholamines and there were no significant changes in blood flow from the output adrenal gland, although in some experiments a slight decrease was recorded. However, administration of PGE2 (1 or 10 µg/kg) into the lumboadrenal artery resulted in a rapid and transient increase in the secretion of both adrenaline and noradrenaline (Fig. la), accom¬ panied by an increase in the rate of adrenal venous blood flow (Fig. lb). A maximum response was observed within 2 min of injection : 1 µg PGE2/kg increased the mean total catecholamine secretion by 421%, compared with the basal rate and the increase after 10 µg/kg was 550%. Adrenal blood flow also increased by 203 and 214% after administration of 1 and Ì0 µg PGE2/ kg respectively. The amount of noradrenaline released, as a percentage of the total secretion 006

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Fig. 1. (a) The rate of secretion of catecholamines and (b) blood flow from the denervated adrenal gland before and up to 32 min after the injection of prostaglandin E2 (PGE2) into the lumboadrenal artery of anaesthetized dogs, (a) Open, hatched and stippled bars, secretion of adrenaline in response to no PGE2 (four dogs), or 1 (ten dogs) or 10 (eight dogs) µg PGE2/kg respectively; black bars, secretion of noradrenaline; (b) O, no PGE2; ·, 1 µg PGE2/kg; , 10 µg PGE2/kg. Values are means±s.e.m.; arrows indicate the time of injection of PGE2 or vehicle. *

Action of prostaglandin E2 on the release of catecholamines from the canine adrenal gland and its interaction with acetylcholine.

ACTION OF PROSTAGLANDIN E2 ON THE RELEASE OF CATECHOLAMINES FROM THE CANINE ADRENAL GLAND AND ITS INTERACTION WITH ACETYLCHOLINE K. YAMASHITA, M...
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