- Email: [email protected]
Vasodilatory effect of pituitary adenylate cyclase activating polypeptide (PACAP) and its related peptides
214 VIP AND RELATED RECEPTORS. Nag~a,S. Osaka BioscienceInstitute, Osaka565, Japan. V a s o a c t i v e intestinal p o l y p e p t i d e (VIP) is a 28-amino acid peptide h o r m o n e which plays many p h y s i o l o g i c a l roles in p e r i p h e r a l and central nerve systems. A functional cDNA clone of the VIP r e c e p t o r was isolated from a rat lung cDNA library by cross h y b r i d i z a t i o n with the secretin receptor cDNA. VIP could bind the cloned VIP receptor e x p r e s s e d in mouse COP cells and could s t i m u l a t e the adenyl cyclase through the cloned receptor. The rat VIP receptor consists of 459 amino acids with a c a l c u l a t e d Mr. of 52,054, and contains seven t r a n s m e m b r a n e segments. The VIP receptor is s t r u c t u r a l l y related to the secretin, calcitonine, and p a r a t h y r o i d hormone receptors, but no s i g n i f i c a n t h o m o l o g y was observed with other G - p r o t e i n coupled r e c e p t o r s i n c l u d i n g the putative human "VIP receptor" clone GPRNI. VIP receptor mRNA could be detected in various rat tissues i n c l u d i n g liver, lung, intestines and brain. In situ h y b r i d i z a t i o n revealed that the VIP receptor mRNA is widely d i s t r i b u t e d in the neuronal cells of adult rat brain with a r e l a t i v e l y high e x p r e s s i o n in n e o c o r t e x and hypocampus.
VASODILATORY EFFECT OF PITUITARY ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE (PACAP) AND ITS RELATED PEPTIDES. S. Naruse, T. Ozaki a n d K. Nokihara* National Institute for Physiological Sciences, Okazaki 444, a n d Biotechnology I n s t r u m e n t s D e p a r t m e n t , S h i m a d z u Corporation*, Kyoto 604, J a p a n . The v a s c u l a r effects of PACAP, a new VIP-like n e u r o p e p t i d e , and its related peptides on femoral arterial blood flow were c o m p a r e d in 5 a n e s t h e t i z e d beagle dogs. PACAP38, PACAP38(COOH), and PACAP27, PACAP1-15, PACAP10-20, PACAP27-38, a n d PACAP27-38 NH2 were s y n t h e s i z e d usi ng the Fmoc-strategy. All peptides were purified a n d c h a r a c t e r i z e d by HPLC, sequencing, am i no acid analysis, and FABMS. U nder p e n t o b a r b i t a l an es th es ia, femoral arterial blood flow was m e a s u r e d by an electromagnetic blood flow meter. PACAP a n d its related peptides (0.25, 0.5, 1, 2.5, 5, 10, a n d 25 pmol/kg) dissolved in 1 ml of saline was infused into t he femoral ar ter y t h r o u g h its b r a n c h in 0.5 min. Intra-arterial infusion of PACAP38, PACAP27 an d VIP (0.25-25 pm ol / kg) i n d u c e d d o s e - r e l a t e d i n c r e a s e s in femoral blood flow. The d o s e - p e a k r e s p o n s e curve for PACAP27 or PACAP38 was similar to t h a t for VIP b u t the r e s p o n s e to PACAP38 at 25 p m o l / k g was significantly less t h a n the others. Vasodflatory effect of PACAP38, however, lasted 3-4 times longer t h a n t h a t of PACAP27 or VIP. Acid form of PACAP38 was similar to PACAP38 in its v a s c u l a r effect. PACAP27-38 a n d PACAP27-38 NH2 at 1 n m o l / k g i n c r e a s e d femoral flow b u t PACAP1-15 a n d PACAP10-20 were w i t h o u t effects. T hus , PACAP38 and PACAP27 are p o t e n t VIP-like vasodilators of femoral a r t e r y in dogs. PACAP38, b u t n o t PACAP27, differs from VIP in its prolonged vasodilatory effect.
VASODILATORY EFFECT OF PITUITARY ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE (PACAP) AND ITS RELATED PEPTIDES. S. Naruse, T. Ozaki a n d K. Nokihara* National Institute for Physiological Sciences, Okazaki 444, a n d Biotechnology I n s t r u m e n t s D e p a r t m e n t , S h i m a d z u Corporation*, Kyoto 604, J a p a n . The v a s c u l a r effects of PACAP, a new VIP-like n e u r o p e p t i d e , and its related peptides on femoral arterial blood flow were c o m p a r e d in 5 a n e s t h e t i z e d beagle dogs. PACAP38, PACAP38(COOH), and PACAP27, PACAP1-15, PACAP10-20, PACAP27-38, a n d PACAP27-38 NH2 were s y n t h e s i z e d usi ng the Fmoc-strategy. All peptides were purified a n d c h a r a c t e r i z e d by HPLC, sequencing, am i no acid analysis, and FABMS. U nder p e n t o b a r b i t a l an es th es ia, femoral arterial blood flow was m e a s u r e d by an electromagnetic blood flow meter. PACAP a n d its related peptides (0.25, 0.5, 1, 2.5, 5, 10, a n d 25 pmol/kg) dissolved in 1 ml of saline was infused into t he femoral ar ter y t h r o u g h its b r a n c h in 0.5 min. Intra-arterial infusion of PACAP38, PACAP27 an d VIP (0.25-25 pm ol / kg) i n d u c e d d o s e - r e l a t e d i n c r e a s e s in femoral blood flow. The d o s e - p e a k r e s p o n s e curve for PACAP27 or PACAP38 was similar to t h a t for VIP b u t the r e s p o n s e to PACAP38 at 25 p m o l / k g was significantly less t h a n the others. Vasodflatory effect of PACAP38, however, lasted 3-4 times longer t h a n t h a t of PACAP27 or VIP. Acid form of PACAP38 was similar to PACAP38 in its v a s c u l a r effect. PACAP27-38 a n d PACAP27-38 NH2 at 1 n m o l / k g i n c r e a s e d femoral flow b u t PACAP1-15 a n d PACAP10-20 were w i t h o u t effects. T hus , PACAP38 and PACAP27 are p o t e n t VIP-like vasodilators of femoral a r t e r y in dogs. PACAP38, b u t n o t PACAP27, differs from VIP in its prolonged vasodilatory effect.