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Neuropeptide Y-mediated potentiation of vasoconstrictor responses in rat kidney
394
DIMINISHED
CONCENTRATIONS
OF
REGULATORY
PEPTIDES
IN
COLONIC
POLYPS. J. CALAM, S. GUPTA, C. TAIT, M.A. GHATEI, T.E. ADRIAN, J. D O M I N and S.R. BLOOM, Royal Postgraduate Medical School, H a m m e r s m i t h Hospital, Du Cane Road, London WI2 0NN, U.K. Regulatory peptides are present in colonic m u c o s a and m i g h t p l a y a role in e p i t h e l i a l growth and neoplasia. We compared peptide concentrations, measured by r a d i o i m m u n o a s s a y , in colonoscopic biopsies taken from i0 polyps (I villous adenoma, and 9 tubular adenomas) with concentrations in n o r m a l m u c o s a l biopsies taken from 38 subjects. Results are expressed in pmol/g wet weight, mean + SEM. M e a n concentrations of enteroglucagon (EG), peptide YY (PYY) and s o m a t o s t a t i n (SO) w h i c h are p r e s e n t predominantly in endocrine cells, were substantially lower in polyps (P) than in m u c o s a l b i o p s i e s (M) : EG; P: 70+40, M:248+23 (P
N E U R O P E P T I D E Y - M E D I A T E D P O T E N T I A T I O N OF V A S O C O N S T R I C T O R RESPONSES IN R A T KIDNEY. D.V.CARTER,
J.HALLIDAY,
P.E.NASH,
and N . P A Y V A N D I ,
Department of Pharmacology, King's College London, Strand, London WC2R 2LS It has been reported that NPY-mediated potentiation of the vasoconstrictor effects of field stimulation in rabbit ear artery are endothelium-dependent (Daly and Hieble,1987). NPY has also been reported to have direct vasoconstrictor effects in rat kidney (Allen et ai.,1984). The present experiments examine first the question of whether NPY will potentiate ~1-adrenoceptor-mediated (phenylephrine) vasoconstrictor effects in perfused rat kidney preparations and second, whether such potentiation is dependent on a functional endothelium which presumably has the capacity to release the potent peptide vasoconstrictor, endothelin. It was found that NPY in I00 pmol bolus doses produced only marginal increases in perfusion pressure whilst giving marked potentiation of phenylephrine-mediated vasoconstrictor responses. Controlled perfusion with the detergent CHAPS was used to produce functional removal of the endothelium and preliminary findings suggest no absolute requirement for the endothelium in the potentiation phenomenon in the rat kidney. Daly,R.N. & Hieble,J.P.(1987).Eur.J.Pharmac.,138,445-446. Allen,J.M.,Bloom,S.R.,Ledingham,J.G.G & Raine,A.E.G.(1984).J.Physiol.,351,34P
DIMINISHED
CONCENTRATIONS
OF
REGULATORY
PEPTIDES
IN
COLONIC
POLYPS. J. CALAM, S. GUPTA, C. TAIT, M.A. GHATEI, T.E. ADRIAN, J. D O M I N and S.R. BLOOM, Royal Postgraduate Medical School, H a m m e r s m i t h Hospital, Du Cane Road, London WI2 0NN, U.K. Regulatory peptides are present in colonic m u c o s a and m i g h t p l a y a role in e p i t h e l i a l growth and neoplasia. We compared peptide concentrations, measured by r a d i o i m m u n o a s s a y , in colonoscopic biopsies taken from i0 polyps (I villous adenoma, and 9 tubular adenomas) with concentrations in n o r m a l m u c o s a l biopsies taken from 38 subjects. Results are expressed in pmol/g wet weight, mean + SEM. M e a n concentrations of enteroglucagon (EG), peptide YY (PYY) and s o m a t o s t a t i n (SO) w h i c h are p r e s e n t predominantly in endocrine cells, were substantially lower in polyps (P) than in m u c o s a l b i o p s i e s (M) : EG; P: 70+40, M:248+23 (P
N E U R O P E P T I D E Y - M E D I A T E D P O T E N T I A T I O N OF V A S O C O N S T R I C T O R RESPONSES IN R A T KIDNEY. D.V.CARTER,
J.HALLIDAY,
P.E.NASH,
and N . P A Y V A N D I ,
Department of Pharmacology, King's College London, Strand, London WC2R 2LS It has been reported that NPY-mediated potentiation of the vasoconstrictor effects of field stimulation in rabbit ear artery are endothelium-dependent (Daly and Hieble,1987). NPY has also been reported to have direct vasoconstrictor effects in rat kidney (Allen et ai.,1984). The present experiments examine first the question of whether NPY will potentiate ~1-adrenoceptor-mediated (phenylephrine) vasoconstrictor effects in perfused rat kidney preparations and second, whether such potentiation is dependent on a functional endothelium which presumably has the capacity to release the potent peptide vasoconstrictor, endothelin. It was found that NPY in I00 pmol bolus doses produced only marginal increases in perfusion pressure whilst giving marked potentiation of phenylephrine-mediated vasoconstrictor responses. Controlled perfusion with the detergent CHAPS was used to produce functional removal of the endothelium and preliminary findings suggest no absolute requirement for the endothelium in the potentiation phenomenon in the rat kidney. Daly,R.N. & Hieble,J.P.(1987).Eur.J.Pharmac.,138,445-446. Allen,J.M.,Bloom,S.R.,Ledingham,J.G.G & Raine,A.E.G.(1984).J.Physiol.,351,34P