Ghrelin reduces voltage-gated calcium currents in GH₃ cells via cyclic GMP pathways

Ghrelin is an endogenous growth hormone secretagogue (GHS) causing release of GH from pituitary somatotropes through the GHS receptor. Secretion of GH is linked directly to intracellular free Ca²⁺ concentration ([Ca²⁺]i), which is determined by Ca²⁺ influx and release from intracellular Ca²⁺ storage sites. Ca²⁺ influx is via voltage-gated Ca²⁺ channels, which are activated by cell depolarization. The mechanism underlying the effect of ghrelin on voltage-gated Ca²⁺ channels is still not clear. In this report, using whole cell patch-clamp recordings, we assessed the acute action of ghrelin on voltage-activated Ca²⁺ currents in GH₃ rat somatotrope cell line. Ca²⁺ currents were divided into three types (T, N, and L) through two different holding potentials (−80 and −40 mV) and specific L-type channel blocker (nifedipine, NFD). We demonstrated that ghrelin significantly and reversibly decreases all three types of Ca²⁺ currents in GH₃ cells through GHS receptors on the cell membrane and down-stream signaling systems. With different signal pathway inhibitors, we observed that ghrelin-induced reduction in voltage-gated Ca²⁺ currents in GH₃ cells was mediated by a protein kinase G-dependent pathways. As ghrelin also stimulates Ca²⁺ release and prolongs the membrane depolarization, this reduction in voltage-gated Ca²⁺ currents may not be translated into a reduction in [Ca²⁺]i, or a decrease in GH secretion.