AGONISTS FOR NEUROPEPTIDE-Y RECEPTOR SUBTYPES NPY-1 AND NPY-2 HAVE OPPOSITE ACTIONS ON RAT NODOSE NEURON CALCIUM CURRENTS

1. The whole-cell variation of the patch-clamp technique was used to study the effect of neuropeptide Y (NPY) and preferential agonists for the NPY-1 and NPY-2 receptor subtypes on voltage-dependent calcium currents in acutely dissociated postnatal rat nodose ganglion neurons. 2. Both low- and high-threshold calcium current components were present. NPY altered voltage-dependent calcium currents in approximately 50% of neurons studied. NPY (0.1 - 100 nM, ED50 6 nM) decreased the peak amplitude of transient high-threshold calcium currents in approximately 45% of the neurons. NPY ( 100 nM) decreased the peak amplitude of these currents 31 +/- 5% (mean +/- SE). However, in approximately 5% of the neurons NPY (100 nM) caused a reversible and reproducible increase in transient high-threshold calcium currents of 21 +/- 4%. NPY did not affect either transient low-threshold or slowly inactivating high-threshold calcium current components. 3. Application of the C-terminal fragment NPY 13-36 (100 nM), a preferential agonist for NPY-2 receptors, reversibly decreased the peak amplitude of transient high-threshold calcium currents by 26 +/- 5% in 9 of 20 cells (45%). Application of [Pro34]NPY (100 nM), a preferential agonist for NPY-1 receptors, reversibly increased the peak amplitude of transient high-threshold calcium currents 20 +/- 4% in 23 out of 48 neurons (48%). Six of 20 neurons (30%) responded to application of both agonists. Neither the NPY-1 nor NPY-2 agonists affected transient low-threshold or slowly inactivating high-threshold calcium current components. 4. Pretreatment of neurons with pertussis toxin (PTX; 100 ng/ml for 12-24 h) blocked the effects of the both NPY-2 and NPY-1 receptor agonists on voltage-dependent calcium currents. 5. We conclude that postnatal rat nodose neurons differentially express functional NPY-2 and NPY-1 receptors. Binding of NPY to NPY-2 or NPY-1 receptors reduced or enhanced transient high-threshold calcium currents, respectively, via PTX-sensitive pathway(s).