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Neuropeptide Y (NPY) and peptide YY (PYY) effects in the epididymis of the guinea‐pig: evidence of a pre‐junctional PYY‐selective receptor
Author(s) -
Haynes John M.,
Hill Stephen J.,
Selbie Lisa A.
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701544
Subject(s) - peptide yy , neuropeptide y receptor , medicine , endocrinology , stimulation , pancreatic polypeptide , chemistry , antagonist , receptor antagonist , receptor , biology , neuropeptide , glucagon , hormone
1 The effects of peptide YY (PYY), neuropeptide Y (NPY) and structurally related peptides upon field stimulation‐induced and phenylephrine‐mediated contractile responses in the cauda epididymis of the guinea‐pig were investigated. 2 Preparations of cauda epididymis responded to field stimulation with contractions which were completely attenuated by both the neurotoxin, tetrodotoxin (500 n M ), and also by the α‐adrenoceptor antagonist, phentolamine (3 μ M ). PYY ( n =7) and the truncated peptide analogue PYY(3–36) ( n =5) inhibited field stimulation‐induced contractions (pIC 50 +s.e.mean: 8.9±0.2 and 9.4±0.2, respectively). Pancreatic polypeptide (PP, up to 1 μ M , n =6), NPY (up to 100 n M , n =6) and the NPY analogues [Leu 31 ,Pro 34 ]NPY ( n =6) and NPY (13–36) (both up to 1 μ M , n =5) had no significant effect. 3 The NPY Y 1 receptor antagonist BIBP3226 (( R )‐N2‐(diphenylacetyl)‐N[(4‐hydroxyphenyl)‐methyl]‐argininamide) at 750 n M ( n =6) and 7.5 μ M ( n =6) did not affect the PYY‐mediated inhibition of field stimulation‐induced contractions (pIC 50 8.9±0.3 and 9.0±0.3, respectively). In the presence of BIBP3226 (7.5 μ M ), NPY ( n =6) inhibited field stimulation‐induced contractions (pIC 50 8.0±0.2). 4 NPY, PYY and PYY(3–36) inhibited [ 3 H]‐noradrenaline release from preparations of epididymis (pIC 50 values 7.9±0.7, 9.6±0.8 and 10.0±0.9, respectively, all n =6). The agonists PP and [Leu 31 ,Pro 34 ]PYY (both up to 100 n M ) were without significant effect (both n =6). 5 In preparations of cauda epididymis, stimulated with threshold concentrations of the α 1 ‐adrenoceptor agonist, phenylephrine (1 μ M ), both NPY ( n =6) and PYY ( n =7) elicited concentration‐dependent increases in contractile force (with pEC 50 values of 8.9±0.2 and 8.6±0.1, respectively). The effects of both NPY ( n =6) and PYY ( n =6) were antagonized by preincubation with BIBP3226 (75 n M ; apparent p K B ±s.e. values 8.3±1.0 and 8.2±0.6, respectively). The peptide analogues NPY(13–36) ( n =5), PYY (3–36) ( n =7) and [Leu 31 ,Pro 34 ]NPY ( n =5) did not significantly augment responses to threshold concentrations of phenylephrine. 6 These results are consistent with the proposal that distinct NPY receptors mediate the (prejunctional) inhibition of field stimulation‐induced contractions and the (postjunctional) potentiation of responses to phenylephrine in the cauda epididymis of the guinea‐pig. The rank order of agonist potency (NPYPYY≫NPY(13–36), [Leu 31 ,Pro 34 ]NPY and PYY(3–36) and the high potency of BIBP3226 indicate that the postjunctional receptor may be Y 1 ‐like. The rank orders of agonist potency in inhibiting field stimulation‐induced contractile responses and [ 3 H]‐noradrenaline release (PYY(3–36)PYY> NPY≫PP, NPY(13–36), [Leu 31 ,Pro 34 ]NPY and PYY(3–36)PYY>NPY≫;PP,[Leu 31 ,Pro 34 ]PYY, respectively) are consistent with the action of these peptides at a PYY‐preferring receptor subtype, which may be distinct from the presently characterized NPY receptor subtypes.