ABSTRACT

Two types of binding sites have previously been described for neuropeptide Y (NPY), called Y, and Y2 receptors. The intracellular events following Y, receptor activation was studied in the human neuroblastoma cell line SK-N-MC. Both NPY and the specific Y, receptor &and, [I.&r,Prdq]-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, receptor stimulation, by both NPY and [LeuJ1,Prd4]NPY, also inhibited the forskolin-stimulated CAMP production with an EC,, of 3.5 nM. There was a close relation between the receptor binding and the cellular effects as half-maximal displacement of PZsI-TylJ6]monoiodoNPY from the receptor was obtained with 2.1 nM NPY. The Y,-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, receptor stimulation is associated with both mobilization of intracellular calcium and inhibition of adenylate cyclase activity.

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