Ghrelin growth hormone secretagogue receptor, with the "GHS-R1b" splice being inactive) is involved in mediating a wide variety of biological effects of ghrelin, including: stimulation of growth hormone release, increase in hunger, modulation of glucose and lipid metabolism, regulation of gastrointestinal motility and secretion, protection of neuronal and cardiovascular cells, and regulation of immune function. They are present in high density in the hypothalamus and pituitary, on the vagus nerve (on both afferent cell bodies and afferent nerve endings) and throughout the gastrointestinal tract. Ghrelin promotes intestinal cell proliferation and inhibits apoptosis during inflammatory states and oxidative stress. It also suppresses
Growth hormone–releasing hormone in vesicle fusion and release of secretory vesicles containing premade growth hormone. Some Ca influx is also a direct action of cAMP, which is distinct from the usual "cAMP-dependent pathway" of activating "protein kinase A". Activation of GHRHRs by GHRH also conveys opening of Na+ channels by phosphatidylinositol 4,5-bisphosphate, causing cell depolarization. The resultant change in the intracellular voltage opens a voltage-dependent calcium channel, resulting in vesicle fusion and release of GH. The actions of GHRH are opposed by somatostatin (growth-hormone-inhibiting hormone). Somatostatin is released from neurosecretory nerve terminals of periventricular somatostatin neurons, and is carried by the hypothalamo-hypophysial portal