Specific peptidergic innervation of blood vessels in various organs with particular reference to VIP.

302 S p e c i f i c p e p t i d e r g i c i n n e r v a t i o n of b l o o d vessels in various organs w i t h p a r t i c u l a r r e f e r e n c e to VIP. W . G . F O R S S M A N N and M.REINECKE (Institute of Anatomy, U n i v e r s i t y of Heidelberg, FRG). 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) has been d e t e c t e d using i m m u n o h i s t o c h e m i s t r y in nerve fibers i n n e r v a t i n g b l o o d v e s s e l s in various organs. These fibers are located in p e r i v a s c u l a r plexus at the a d v e n t i t i a - m e d i a border. However, other n e u r o p e p t i d e s such as neurotensin (NT), s u b s t a n c e P (SP), s o m a t o s t a t i n (SOM), a n g i o t e n s i n (ANG), p a n c r e a t i c p o l y p e p t i d e (PP), e n k e p h a l i n (ENK) are d e t e c t e d by immunoc y t o c h e m i s t r y in these p e r i v a s c u l a r plexus. N e u r o p e p t i d e s seem to be in the n o n - a d r e n e r g i c and n o n - c h o l i n e r g i c r e g u l a t i o n of c a r d i o v a s c u l a r f u n c t i o n of g r e a t importance. We have studied v a s c u l a r i n n e r v a t i o n w i t h p a r t i c u l a r a t t e n t i o n to p e p t i d e r g i c nerves. V I P - i m m u n o r e a c t i v e (IR) v a r i c o s i t i e s are w i d e l y d i s t r i b u t e d among b l o o d vessels, m a i n l y s u p p l y i n g a r t e r i e s and a r t e r i o l e s in m o s t viscera. They are located around cerebral, cardiac, pulmonary, g a s t r o i n t e s t i n a l , kidney, and g l a n d u l a r arteries and arterioles. A lesser d e n s i t y of V I P - I R nerves is seen a d j a c e n t to veins and venules. In a d d i t i o n to V I P - n e r v e s , o t h e r p e p t i d e s are l o c a l i z e d in p e r i v a s c u l a r plexus. However, they exh i b i t d i f f e r e n t d i s t r i b u t i o n patterns. For example, kidney blood vessels are i n n e r v a t e d by a m o d e r a t e number of SP-IR nerves in the large a r t e r i a l segments, w h e r e a s few S O M - I R and many N T - I R nerves are found. The latter are p r e d o m i n a n t l y located around c o r t i c a l a r t e r i o l a r blood vessels. The p e p t i d e r g i c nerves in the p e r i v a s c u l a r segments in part act v a s o c o n s t r i c t i v e and in part v a s o d i l a t i v e . A few fibers may also be of a f f e r e n t nature. In summary, the i n v e s t i g a t i o n shows that each o r g a n e x h i b i t s a specific p e p t i d e r g i c i n n e r v a t i o n of its supplying b l o o d vessels. This o r g a n specific i n n e r v a t i o n may be r e s p o n s i b l e for c e r t a i n v a s c u l a r r e a c t i o n s under p h y s i o l o g i c a l conditions. S u p p o r t e d by a grant of the G e r m a n R e s e a r c h F o u n d a t i o n ,

SFB 90, Carvas.

Solid-Phase Synthesis Conformational Studies and Biological Activities of VIP and Related Fragments. FOURNIER~ A., SAUNDERS, J.K. and ST-PIERRE, S. (Department of Physiology and Pharmacology and Department of Chemistry, University of Sherbrooke, Sherbrooke, Quebec, Canada JIH 5N4).

VIP and related fragments were prepared by the solid-phase method. The synthesis w~s performed on benzhydrylamine resin and the couplings of the Boo-amine acids were carried out by the symmetrical anhydride method. Cleavage was achieved by treatment with liquid HF and purification was accomplished by successive steps of cation exchange, partition and semi-preparative high pressure liquid chromatography. The coumpounds were characterized by thin-layer chromatography, amino acid analysis and analytical hplc. The biological activities of the peptides were evaluated in v i t r o on the rabbit perfused heart and i n v i v o on the rat blood pressure. Structural studies were performed by high resolution (400 MHz) IH NMR spectroscopy and circular dichroism. Attempts have been made to correlate results of the conformational and biological studies, The results show that among all the fragments tested, only VIP2-28 retains significant biological activity. The fragments devoid of activity were found to be inactive as antagonists. VIP and some fragments tend to adopt the helical structure, as demonstrated by spectroscopic techniques.