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Secretin provocation test in the diagnosis of gastrinomas and other forms of hypergastrinaemia
858
TWO DIFFERENT STATES OF ACTIVATION OF CHOLECYSTOKININ (CCK) RECEPTORS ON PANCREATIC ACINAR CELLS, R.T. Jensen, G.F. Lemp and J.D. Gardner. NIH, Bethesda, Md., 20205, U.S.A. In dispersed acini from guinea pig pancreas, the dose-response curve for CCKstimulated enzyme secretion is biphasic in that as the CCK concentration is increased, e~zyme secretion increases, becomes maximal and then decreases to a plateau. In the present studies we compared the abilities of various Cterminal fragments of CCK to bind to CCK receptors (determined using 1251-CCK) with their abilities to stimulate amylase secretion. CCK as well as CCK-8, CCK-7, CCK-6, CCK-5 and CCK-4 were able to bind to the CCK-receptors and the dose-response curve for each fragment was parallel to that for CCK. With CCK, CCK-8 or CCK-7 the dose-response curve for stimulation of amylase secretion was biphasic. CCK-5 or CCK-4 had the same efficacy as CCK, but the dose-response curve did not decrease with supramaximal concentrations. CCK-6, also had the same efficacy for enzyme secretion as CCK, but the magnitude of the reduction with supramaximal concentrations was only 50% of that obtained with CCK. CCK-5 and CCK-4 competitively inhibited the reduction in the stimulation of amylase secretion caused by supramaximal concentrations of CCK. These results indicate that two different states of stimulation of enzyme secretion can occur as a result of occupation of the CCK receptor. One state is characteristized by full stimulation of enzyme secretion and can be produced by any fragment of CCK containing the C-terminal tetrapeptide. The other state is characterized by restricted stimulation of enzyme secretion and can be produced only by fragments of CCK that contain the C-terminal heptapeptide. CCK-6 is a partial agonist for causing restricted stimulation, whereas CCK-5 and CCK-4, although they are able to occupy the receptors, are unable to cause restricted stimulation; and therefore, function as competitive antagonists of those peptides that can cause restricted stimulation.
S E C R E T I N P R O V O C A T I O N TEST IN THE D I A G N O S I S OF G A S T R I N O M A S AND O T H E R FORMS OF H Y P E R G A S T R I N A E M I A . S.N. Joffe, J.N. P r i m r o s e and J.G. Rateliffe. G l a s g o w Royal Inf. The s e c r e t i n p r o v o c a t i o n test is r e p o r t e d to be a r e l i a b l e test for g a s t r i n o m a and a g r e a t e r than 50% rise in the p l a s m a g a s t r i n level is said to be d i a g n o s t i c of a gastrinoma. We have p e r f o r m e d the s e c r e t i n p r o v o c a t i o n test in the f o l l o w i n g situations, g a s t r i n -omas (n=3), r e c u r r e n t peptic u l c e r (n=50), s y m p t o m a t i c p a t i e n t s f o l l o w i n g DU surgery (n=20), u n o p e r a t e d p r i m a r y DU (n=lO), pernicious a n a e m i a (n=2) and c o n t r o l s (n=10). Tests were p o s i t i v e (rise of g r e a t e r than 50) in all p a t i e n t s w i t h g a s t r i n o m a who also had e l e v a t e d basal p l a s m a gastrin. S i x t e e n of the 50 r e c u r r e n t u l c e r p a t i e n t s had +ve tests, 6 had an e l e v a t e d basal g a s t r i n but only one s u b s e q u e n t l y was shown to have a gastrinoma. Two a s y m p t o m a t i c post DU s u r g e r y p a t i e n t s had +ve tests w i t h normal basal gastrin. Four p r i m a r y DU p a t i e n t s had a +re test but none had an e l e v a t e d basal g a s t r i n level and none of the i0 control p a t i e n t s had ~ve tests. The 2 p a t i e n t s w i t h p e r n i c i o u s a n a e m i a had h y p e r g a s t r i n ae m i a and no r e s p o n s e to secretin. It is c o n c l u d e d that a l t h o u g h the s e c r e t i n p r o v o c a t i o n test is +re in g a s t r i n o m a p a t i e n t s it is also f r e q u e n t l y p o s i t i v e in other DU patients. R e g a r d l e s s of the c r i t e r i a u s e d it is not a r e l i a b l e test for the c o n c l u s i v e d i a g n o s i s of a gastrinoma.
TWO DIFFERENT STATES OF ACTIVATION OF CHOLECYSTOKININ (CCK) RECEPTORS ON PANCREATIC ACINAR CELLS, R.T. Jensen, G.F. Lemp and J.D. Gardner. NIH, Bethesda, Md., 20205, U.S.A. In dispersed acini from guinea pig pancreas, the dose-response curve for CCKstimulated enzyme secretion is biphasic in that as the CCK concentration is increased, e~zyme secretion increases, becomes maximal and then decreases to a plateau. In the present studies we compared the abilities of various Cterminal fragments of CCK to bind to CCK receptors (determined using 1251-CCK) with their abilities to stimulate amylase secretion. CCK as well as CCK-8, CCK-7, CCK-6, CCK-5 and CCK-4 were able to bind to the CCK-receptors and the dose-response curve for each fragment was parallel to that for CCK. With CCK, CCK-8 or CCK-7 the dose-response curve for stimulation of amylase secretion was biphasic. CCK-5 or CCK-4 had the same efficacy as CCK, but the dose-response curve did not decrease with supramaximal concentrations. CCK-6, also had the same efficacy for enzyme secretion as CCK, but the magnitude of the reduction with supramaximal concentrations was only 50% of that obtained with CCK. CCK-5 and CCK-4 competitively inhibited the reduction in the stimulation of amylase secretion caused by supramaximal concentrations of CCK. These results indicate that two different states of stimulation of enzyme secretion can occur as a result of occupation of the CCK receptor. One state is characteristized by full stimulation of enzyme secretion and can be produced by any fragment of CCK containing the C-terminal tetrapeptide. The other state is characterized by restricted stimulation of enzyme secretion and can be produced only by fragments of CCK that contain the C-terminal heptapeptide. CCK-6 is a partial agonist for causing restricted stimulation, whereas CCK-5 and CCK-4, although they are able to occupy the receptors, are unable to cause restricted stimulation; and therefore, function as competitive antagonists of those peptides that can cause restricted stimulation.
S E C R E T I N P R O V O C A T I O N TEST IN THE D I A G N O S I S OF G A S T R I N O M A S AND O T H E R FORMS OF H Y P E R G A S T R I N A E M I A . S.N. Joffe, J.N. P r i m r o s e and J.G. Rateliffe. G l a s g o w Royal Inf. The s e c r e t i n p r o v o c a t i o n test is r e p o r t e d to be a r e l i a b l e test for g a s t r i n o m a and a g r e a t e r than 50% rise in the p l a s m a g a s t r i n level is said to be d i a g n o s t i c of a gastrinoma. We have p e r f o r m e d the s e c r e t i n p r o v o c a t i o n test in the f o l l o w i n g situations, g a s t r i n -omas (n=3), r e c u r r e n t peptic u l c e r (n=50), s y m p t o m a t i c p a t i e n t s f o l l o w i n g DU surgery (n=20), u n o p e r a t e d p r i m a r y DU (n=lO), pernicious a n a e m i a (n=2) and c o n t r o l s (n=10). Tests were p o s i t i v e (rise of g r e a t e r than 50) in all p a t i e n t s w i t h g a s t r i n o m a who also had e l e v a t e d basal p l a s m a gastrin. S i x t e e n of the 50 r e c u r r e n t u l c e r p a t i e n t s had +ve tests, 6 had an e l e v a t e d basal g a s t r i n but only one s u b s e q u e n t l y was shown to have a gastrinoma. Two a s y m p t o m a t i c post DU s u r g e r y p a t i e n t s had +ve tests w i t h normal basal gastrin. Four p r i m a r y DU p a t i e n t s had a +re test but none had an e l e v a t e d basal g a s t r i n level and none of the i0 control p a t i e n t s had ~ve tests. The 2 p a t i e n t s w i t h p e r n i c i o u s a n a e m i a had h y p e r g a s t r i n ae m i a and no r e s p o n s e to secretin. It is c o n c l u d e d that a l t h o u g h the s e c r e t i n p r o v o c a t i o n test is +re in g a s t r i n o m a p a t i e n t s it is also f r e q u e n t l y p o s i t i v e in other DU patients. R e g a r d l e s s of the c r i t e r i a u s e d it is not a r e l i a b l e test for the c o n c l u s i v e d i a g n o s i s of a gastrinoma.