Neuropeptide Y regulates intracellular calcium through different signalling pathways linked to a Y-1-receptor in rat mesenteric small arteries

1 Simultaneous measurements of intracellular calcium concentration ([Ca2+]( i)) and tension were performed to clarify whether the mechanisms which caus e the neuropeptide Y (NPY)-elicited contraction and potentiation of noradre naline contractions, and the NPY inhibition of forskolin responses are link ed to a single or different NPY receptor(s) in rat mesenteric small arterie s. 2 In resting arteries, NPY moderately elevated [Ca2+](i) and tension. These effects were antagonized by the selective Y-1 receptor antagonist, (R)-N-2 -(diphenacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginineamide (BIBP 3226) (ap parent pK(B) values of 8.54 +/- 0.25 and 8.27 +/- 0.17, respectively). 3 NPY (0.1 mu M) caused a near 3 fold increase in sensitivity to noradrenal ine but did not significantly modify the tension-[Ca2+](i) relationship for this agonist. BIBP 3226 competitively antagonized the contractile response to NPY in arteries submaximally preconstricted with noradrenaline (pA(2) 7 .87 +/- 0.20). 4 In arteries activated by vasopressin, the adenylyl cyclase activator fors kolin (3 mu M) induced a maximum relaxation and a return of [Ca2+](i) to re sting levels. NPY completely inhibited these effects. The contractile respo nses to NPY in arteries maximally relaxed with either sodium nitroprusside (SNP) or nifedipine were not significantly higher than those evoked by the peptide at resting tension, in contrast to the contractions to NPY in forsk olin-relaxed arteries. BIBP 3226 competitively antagonized the contraction to NPY in forskolin-relaxed arteries with a pA(20) of 7.92 +/- 0.29. 5 Electrical field stimulation (EFS) at 8-32 Hz caused large contractions i n arteries relaxed with either forskolin or noradrenaline in the presence o f phentolamine. These responses to EFS were inhibited by BIBP 3226. Similar EFS in resting, non-activated arteries did not produce any response. 6 The present results suggest that different intracellular pathways are lin ked to a single NPY Y-1 receptor in intact rat mesenteric small arteries, a nd provide little support for involvement of other postjunctional NPY recep tors in the contractile responses to NPY. Neurally released NPY also seems to act through Y-1 receptors, and may serve primarily as an inhibitor of va sodilatation.