- Email: [email protected]
Ontogeny of glucagon-containing peptides in the entero-pancreatic tract of the rat
164 F I R S T PASS U P T A K E OF V A S O A C T I V E I N T E S T I N A L THE P O R C I N E P U L M O N A R Y C I R C U L A T I O N
POLYPEPTIDE
(VIP)
IN
D. H V I D S T E N , R.O. L I N D S E T M O , O. R@KKE, T.G. J E N S S E N , P.G. B U R H O L and A. R E V H A U G , I n s t i t u t e of C l i n i c a l M e d i c i n e , U n i v e r s i t y of Troms~, N-9001 Troms~, Norway To d e t e r m i n e the f i r s t pass u p t a k e of v a s o a c t i v e i n t e s t i n a l p o l y p e p t i d e (VIP) in the p o r c i n e lung, VIP (9 p m o l ' k g -l) and i n d o c y a n i n e g r e e n (ICG) w e r e g i v e n as a bolus into the r i g h t atrium. Simultaneously, blood was w i t h d r a w n from the p u l m o n a r y a r t e r y for 15 s, c o r r e s p o n d i n g to the r e c i r c u l a t i o n time. The s a m p l i n g from the a o r t a was s i m i l a r , but was d e l a y e d 3 s, c o r r e s p o n d i n g to the t r a n s p u l m o n a r y c i r c u l a t i o n time. ICG is a s u b s t a n c e w h i c h is k n o w n to pass t h r o u g h the p u l m o n a r y c i r c u l a tion w i t h o u t any d e g r a d a t i o n or u p t a k e . The r e l a t i o n s h i p b e t w e e n the p l a s m a l e v e l s of VIP and ICG was c o m p a r e d in the p u l m o n a r y a r t e r y and the a o r t a . The V I P / I C G q u o t i e n t was s i g n i f i c a n t l y s m a l l e r in the aorta, thus, the c a l c u l a t e d first pass u p t a k e of VIP was 36 + 6%. The u p t a k e m e c h a n i s m s w e r e not s a t u r a t e d by a c o n t i n u o u s TIP i n f u s i o n (3 p m o l . k g - l . m i n -l) s i n c e the first pass u p t a k e was u n c h a n g e d (36 ~ 13%). The p l a s m a l e v e l s in the p u l m o n a r y a r t e r y and a o r t a d u r i n g c o n t i n u o u s i n f u s i o n w e r e 24 2 p m o l . l - I and 20 + 1 p m o l . l -I, resp. The d i f f e r e n c e was s i g n i f i c a n t ( p < O . O O O 1 ) , in c o n t r a s t to the d i f f e r e n c e in b a s e l i n e l e v e l s . We c o n c l u d e that the lung does not r e l e a s e VIP d u r i n g b a s e l i n e c o n d i t i o n s . The p u l m o n a r y c i r c u l a t i o n is a s u b s t a n t i a l c o n t r i b u t o r to the r e m o v a l of VIP from p l a s m a .
ONTOGENY OF GLUCAGON-CONTAINING PEPTIDES IN THE ENTERO-PANCREATIC TRACT OF THE RAT. A. KERVRAN, P. BLACHE, A.M. DELAUNAY and D. BATAILLE, Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Rue de la Cardonille, 34094 Montpellier cedex 2, France. The development of glucagon-containing peptides in the rat foetus is not fully understood. Yet, in the intestinal tract, glucagon-like immunoreactive peptides with 11-12 and 5-6 kDaltons have been described from day 18 of gestation onwards 1 and in the pancreas, glicentin-like material was found by immunocytochemistry on day 182. To precise further the molecular forms related to the glucagon-like imrnunoreactivity, we have investigated the ontogeny of glicentin, oxyntomodulin and glucagon in the entero- pancreatic tract of the rat, between day 11 of gestation and the postnatal day 8. Heat-coagulation extracts were analysed by high performance liquid chromatography coupled to radioimmunoassays using a centrally-directed glucagon antiserum and a C-terminal glicentin / oxyntomodulin antiserum. In the intestine, glicentin, oxyntomodulin and glucagon were detectable on day 16 of gestation onwards. Their concentrations increased 250-fold up to postnatal day 8 and then 2-fold up to the adult age. The percentages of the 3 peptides were stable at all ages studied (34_+2%, 63+9.% and 3+1%, respectively) and in the range of those found in the adult (38+1%, 595:1% and 1.3_+0.1%). In the pancreas, oxyntomodulin and glucagon were found on day 12 of gestation. Their quantities were increased 20-fold between day 12 and day 20 of gestation to reach values 500-fold higher in the adult pancreas.The percentage of oxyntomodulin was close to 10% at all ages studied and was similar to that observed in the adult. At all stages, glicentin was undetectable. These results suggest that the processing of proglucagon appeared early in the foetal period, as soon as the main end-products glicentin, oxyntomodulin and glucagon could be detected and that this processing is similar to that found in the adult. 1 Brubaker P.L. Reg. Peptides, 17, 319-326 (1987) 2 Larsson L.I. et al. J. Histochem. Cytochem., 28, 925-933 (1980)
POLYPEPTIDE
(VIP)
IN
D. H V I D S T E N , R.O. L I N D S E T M O , O. R@KKE, T.G. J E N S S E N , P.G. B U R H O L and A. R E V H A U G , I n s t i t u t e of C l i n i c a l M e d i c i n e , U n i v e r s i t y of Troms~, N-9001 Troms~, Norway To d e t e r m i n e the f i r s t pass u p t a k e of v a s o a c t i v e i n t e s t i n a l p o l y p e p t i d e (VIP) in the p o r c i n e lung, VIP (9 p m o l ' k g -l) and i n d o c y a n i n e g r e e n (ICG) w e r e g i v e n as a bolus into the r i g h t atrium. Simultaneously, blood was w i t h d r a w n from the p u l m o n a r y a r t e r y for 15 s, c o r r e s p o n d i n g to the r e c i r c u l a t i o n time. The s a m p l i n g from the a o r t a was s i m i l a r , but was d e l a y e d 3 s, c o r r e s p o n d i n g to the t r a n s p u l m o n a r y c i r c u l a t i o n time. ICG is a s u b s t a n c e w h i c h is k n o w n to pass t h r o u g h the p u l m o n a r y c i r c u l a tion w i t h o u t any d e g r a d a t i o n or u p t a k e . The r e l a t i o n s h i p b e t w e e n the p l a s m a l e v e l s of VIP and ICG was c o m p a r e d in the p u l m o n a r y a r t e r y and the a o r t a . The V I P / I C G q u o t i e n t was s i g n i f i c a n t l y s m a l l e r in the aorta, thus, the c a l c u l a t e d first pass u p t a k e of VIP was 36 + 6%. The u p t a k e m e c h a n i s m s w e r e not s a t u r a t e d by a c o n t i n u o u s TIP i n f u s i o n (3 p m o l . k g - l . m i n -l) s i n c e the first pass u p t a k e was u n c h a n g e d (36 ~ 13%). The p l a s m a l e v e l s in the p u l m o n a r y a r t e r y and a o r t a d u r i n g c o n t i n u o u s i n f u s i o n w e r e 24 2 p m o l . l - I and 20 + 1 p m o l . l -I, resp. The d i f f e r e n c e was s i g n i f i c a n t ( p < O . O O O 1 ) , in c o n t r a s t to the d i f f e r e n c e in b a s e l i n e l e v e l s . We c o n c l u d e that the lung does not r e l e a s e VIP d u r i n g b a s e l i n e c o n d i t i o n s . The p u l m o n a r y c i r c u l a t i o n is a s u b s t a n t i a l c o n t r i b u t o r to the r e m o v a l of VIP from p l a s m a .
ONTOGENY OF GLUCAGON-CONTAINING PEPTIDES IN THE ENTERO-PANCREATIC TRACT OF THE RAT. A. KERVRAN, P. BLACHE, A.M. DELAUNAY and D. BATAILLE, Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Rue de la Cardonille, 34094 Montpellier cedex 2, France. The development of glucagon-containing peptides in the rat foetus is not fully understood. Yet, in the intestinal tract, glucagon-like immunoreactive peptides with 11-12 and 5-6 kDaltons have been described from day 18 of gestation onwards 1 and in the pancreas, glicentin-like material was found by immunocytochemistry on day 182. To precise further the molecular forms related to the glucagon-like imrnunoreactivity, we have investigated the ontogeny of glicentin, oxyntomodulin and glucagon in the entero- pancreatic tract of the rat, between day 11 of gestation and the postnatal day 8. Heat-coagulation extracts were analysed by high performance liquid chromatography coupled to radioimmunoassays using a centrally-directed glucagon antiserum and a C-terminal glicentin / oxyntomodulin antiserum. In the intestine, glicentin, oxyntomodulin and glucagon were detectable on day 16 of gestation onwards. Their concentrations increased 250-fold up to postnatal day 8 and then 2-fold up to the adult age. The percentages of the 3 peptides were stable at all ages studied (34_+2%, 63+9.% and 3+1%, respectively) and in the range of those found in the adult (38+1%, 595:1% and 1.3_+0.1%). In the pancreas, oxyntomodulin and glucagon were found on day 12 of gestation. Their quantities were increased 20-fold between day 12 and day 20 of gestation to reach values 500-fold higher in the adult pancreas.The percentage of oxyntomodulin was close to 10% at all ages studied and was similar to that observed in the adult. At all stages, glicentin was undetectable. These results suggest that the processing of proglucagon appeared early in the foetal period, as soon as the main end-products glicentin, oxyntomodulin and glucagon could be detected and that this processing is similar to that found in the adult. 1 Brubaker P.L. Reg. Peptides, 17, 319-326 (1987) 2 Larsson L.I. et al. J. Histochem. Cytochem., 28, 925-933 (1980)