Low potency inhibition of Ca channel currents in human neuroblastoma (SH-SY5Y) cells by [Ala]NPY, an l-alanine substituted analogue of neuropeptide Y

Whole-cell Ca²⁺ channel currents were recorded in human neuroblastoma (SH-SY5Y) cells, using the perforated-patch technique with 10 mM Ba²⁺ as charge carrier. Neuropeptide Y (NPY; 10 nM to 1 μM) caused concentration-dependent inhibition of Ca²⁺ channel currents which were associated with a slowing in current activation kinetics. [Ala³¹]NPY, a residue 31 l-alanine substituted analogue of NPY, also inhibited Ca²⁺ channel currents and caused slowing of activation kinetics, but with approximately 6-fold lower potency. In the presence of 100 nM [Ala³¹]NPY (which itself had little or no effect on currents), the actions of NPY were similar in magnitude to its effects in the absence of the analogue. Our results suggest that substitution of isoleucine for alanine at residue 31 results in a NPY analogue which is a full agonist but with lower affinity for Y₂ receptors.