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Y 1 receptors for neuropeptide Y are coupled to mobilization of intracellular calcium and inhibition of adenylate cyclase
Author(s) -
Aakerlund Lars,
Gether Ulrik,
Fuhlendorff Jannie,
Schwartz Thue W.,
Thastrup Ole
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)80069-u
Subject(s) - neuropeptide y receptor , calcium , receptor , endocrinology , medicine , chemistry , calcium in biology , forskolin , egta , intracellular , biology , biochemistry , neuropeptide
Two types of binding sites have previously been described for neuropeptide Y (NPY), called Y 1 and Y 2 receptors. The intracellular events following Y 1 , receptor activation was studied in the human neuroblastoma cell line SK‐N‐MC. Both NPY and the specific Y 1 receptor ligand, [Leu 31 ,Pro 34 ]‐NPY, caused a rapid and transient increase in the concentration of free calcium in the cytoplasm as measured by the fluorescent probe, Fura‐2. The effect of both peptides was independent of extracellular calcium as addition of EGTA or manganese neither changed the size nor the shape of the calcium response. The calcium response to NPY was abolished by pretreatment with thapsigargin, which can selectively deplete a calcium store in the endoplasmic reticulum. Y 1 receptor stimulation, by both NPY and [Leu 31 ,Pro 34 ]NPY, also inhibited the forskolin‐stimulated cAMP production with an EC 50 of 3.5 nM. There was a close relation between the receptor binding and the cellular effects as half‐maximal displacement of [ 125 I‐Tyr 36 ] monoiodoNPY from the receptor was obtained with 2.1 nM NPY. The Y 2 ‐specific ligand NPY(16–36)peptide had no effect on either intracellular calcium or cAMP levels in the SK‐N‐MC cells. It is concluded that Y 1 receptor stimulation is associated with both mobilization of intracellular calcium and inhibition of adenylate cyclase activity.