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NERVOUS RELEASE OF VIP FROM THE FELINE UTERUS: PHARMA(X)LOGICAL CHARACI~'I- STICS. Jan Fahrenkrug and Bent Ottesen, Department of Clinical Chemistry, Glostrup Hospital, University of Copenhagen, DK-2600 Glostrup, Copenhagen, Denmark. VIP-iraaunoreactive nerve fibres are present in the female genital tract ha- ving a close relation to vascular and non-vascular smooth muscle as well as epithelial cells. The VIPergic nerves in the uterus seem to originate fr~n cell bodies located in ganglia of the paracervical tissue at the uterovaginal junction. Since these ganglia receive innervation from the pelvic and hypo- gastric nerves we decided to examine if electrical stimulation of the pel- vic and hypogastric nerves could provoke a VIP release from the uterus of anaesthetized cats. Efferent high threshold stimulation of the pelvic or the hypogastric nerves caused a marked increase in the release of VIP to the local venous effluent. Upon pelvic nerve stirmdation uterine VIP output increased from 0.9 fmol x min.-±(0.5-1.3) to a peak value of 15.3 f~ol x min.- (3.3-54.0) i0 min. after the onset of the nervous activation, while a~ter hypogastric nerve stimulation a higher peak value (50.7 f~ol x min. -~ (16.1-104.4) was ob- tained already after 5 min..The neurally induced VIP responses were unaffec- ted by local administration of atropine and adrenoceptor antagonists, but ccmpletely abolished by hexamethoni~n. After atropine and adrenoceptor blockade the VIP release in response to hypogastric nerve stimulation was -i acccmpanied by an increase ~n uterine venous blood flow from i. 3 ml x min. (0.5-2.0) to 1.6 ml x min.- (1.2-3.8) The results suggest that the VIPergic neurones in the uterus are under pre- ganglionic cholinergic influence of pelvic and hypogastric nervous activity. In the view of the vasodilatory action of VIP in the uterus and the vascular localization of the VIPergic nerve terminals it is proposed that VIP plays a role as transmitter substance in non-cholinergic, non-adrenergic control of uterine blood flow.

RELEASE OF GASTRIN AND SECRETIN DURING ANTACID TREATMENT. F.Halter, W.Reinhart, L.Varga, Gastrointestinal Unit, University Hospital, Inselspital, 3010 Berne, Switzerland. To obtain more information on the mechanisms controlling the release of gas- trin and secretin during antacid treatment we correlated intragastric pH to RIA gastrin and secretin levels after food (study I) or Hp-stimulation by im- promidine (study II). The antacids administered, Alueol R ~A)~and Syntrogel R

(S) are both magnesiumaaluminium-hydroxide mixtures but S is supplemented by

calcium carbonate. In both studies i0 volunteers each received either 30 ml of A, S or placebo (P) 30 minutes after each of three regular meals (study I) or 60 ml one hour after the onset of a i0 ~g/kg/h impromidine infusion. Parallel i0 sets of data on serum-magnesium, ealcium, gastrinrseeretin and gastric pH

were sampled in study I, five in study II. During food stimulation (study I) either A or S enhanced the integrated serum gastrin response to above control levels (A: 86.2+--11.9 pmol.h/l, S: 90.5+--11.0 compared to P: 55.6~6.0, p<0.05) but were similar for all treatments in study II. In contrast, integrated se- cretin response was only influenced by antacid treatment in the impromidine study (A: 4.28~0.48 pmol. h/l, S: 4.35~0.43, P: 6.16~0.44, p<0.01). There was overall positive correlation between serum gastrin and pH after food stimula- tion (n=80, P: r=0.32, p<0.01, A: r=0.61, p<0.001, S: r=0.42, p<0.001) and a negative one between serum secretin and gastric pH for A and S after impromi- dine stimulation (n=50, A: r=0.43, p<0.005, S: r=0.45, p<0.01). The treatment had no influence on the slope of the regression lines. Antacid administration resulted in a slight, significant increase in serum magnesium levels after A and S and in serum calcium after S.

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Conclusion: when antacids are administered postprandially, the effect on gas-

tric pH is of major importance for serum gastrin release and not the presence

or absence of calcium. This is similar for secretin in the absence of food.

H~-ANTAGONISTS IN THE MANAGEMENT OF ZOLLINGER-ELLISON SYNDROME: A COMBINED TMERAPEUTIC APPROACH. S. Bonf i l s , M. Mignon, T. Va l lo t , Ph. Hervoir , P. Benfredj. H6p. Bichat, 75877 Paris Cedex 18, France

In 28 cases of Zo l l i nge r -E l l i son syndrome (ZES), H~-antagonists were tested and used as maintenance treatment: a management st rategy was devised based on a) c l i n i c a l and endoscopic c r i t e r i a of drug e f f i cacy , b) successful attempt at tumor exc is ion. The studied population was not s i g n i f i c a n t l y d i f f e ren t from a reference population ( I ) const i tu ted of 92 su rg i ca l l y t reated cases without H2-antagonist adminis t rat ion in the fo l lowing points: age, sex r a t i o , primary upper GI lesions (41.4 %), recurrent peptic ulcer (25 %), diarrhea (57 %). Serum gast r in and/or secret in provocation tests were abnormal in every pat ient while a gastrinoma was found in 22 pat ients . Cimetidine alone was used at a d a i l y dosage of 1 to 2.4 g (13 cases); r a n i t i d i n e 0.6 to 1.2 g da i l y was used in 15 cases, fo l lowing i n i t i a l treatment with c imet id ine. Successful response to H~-antagonists was obtain- ed in 12 cases: th i s allowed attempt at tumor ~xcis ion resu l t ing in a d e f i n i t e cure of the syndrome in 4 cases ( fo l low-up 4 months to 5 years) . Three other cases were t reated by to ta l gastrectomy. The las t 5 cases are s t i l l under maintenance therapy ( fo l low-up 1 to 3 years) e i the r with c imet i - dine (2 cases) or r a n i t i d i n e (3 cases). I n i t i a l unsat is fac tory response to Hp-antagonists leading to to ta l gastrectomy was observed in 9 cases inc lu - ding 2 acute presentat ions. F i na l l y , in 7 cases maintenance therapy was undertaken without attempting tumoral excis ion ( large size tumor, extensive l i v e r metastases): in 6 pat ients , adequate control of symptoms and gast r ic secret ion as estimated on 24-hr p ro f i l e s was obtained ( fo l low-up 1 to 5 years) with the f i n a l use of r a n i t i d i n e (0.6 g, 2 cases; 0.9 g, 3 cases; 1.2 g, 1 case). Subst i tu t ion of r a n i t i d i n e to c imet id ine was decided on the basis of untoward side e f fec ts and/or drug secondary i ne f f i cacy . Neither l i v e r metastases nor p r io r vagotomy seem to define a spec i f i c response to Hp-antagonists. We conclude that in the management of ZES H~-antagonists most be used in 2 main condi t ions: l ) as an ant isecre tory ~overage for attempting tumor excis ion without gas t r ic surgery, 2) as a maintenance therapy capable of avoiding to ta l gastrectomy i f monitored by repeated adequate tes t ings . ( I ) Bonf i ls S. et a l . : Ann Surg 1981, 194:692-697

CLINICAL APPLICATION OF THE ATROPINE TEST FOR DIAGNOSIS OF PANCREATIC

Pp'OMAS

Adrian T.E. & Bloom S.R. Department of Medicine, Royal Postgraduate Medical School, Hammersmith

Hospital, London W12 OHS, UK. To date there have been few genuine routine clinical applications of the measurement of gut hormones. We have run a weekly pancreatic endocrine tumour screen for several years. A common problem is moderate elevation of

plasma PP concentrations which may be due to an apudema or, alternatively, to a variety of other diseases, eg. diabetes, renal impairment, infections,

stress, chronic alcohol abuse or old age. As normally PP release is dependent on the cholinergic innervation it has been suggested that atropine administration should distinguish between autonomous PP secretion

by tumours and normal PP release, which is always suppressible by atropine (Schwartz T.W. Lancet II: 43-44, 1978). The effect of atropine (img, im) on plasma PP concentrations was investigated in 12 patients with pancreatic