Experimental evidence supporting the scheme presented in fig 4
| Step | Event | Reference |
|---|---|---|
| NPY, neuropeptide Y; AgRP agouti related peptide; icv, intracerebroventricular. | ||
| The step numbers refer to fig 4. | ||
| 1 | During fasting plasma ghrelin increases | 20 |
| 1 | Following gastrectomy plasma ghrelin decreases dramatically | 18 |
| 2 | Small amounts of ghrelin may pass the blood brain barrier, and the arcuate nucleus does not have a blood brain barrier | 19 (review) |
| 3 | Ghrelin receptors are present in the nodose ganglion | 30 |
| 3 | Ghrelin (icv) activates neurones in the dorsomotor nucleus | 31 |
| 3 | Vagotomy or application of the neurotoxin capsaicin on vagal terminals inhibits the effect of ghrelin | 32 |
| 4 | Ghrelin (iv) activates NPY and AgRP neurones in the arcuate nucleus | 33 |
| 4 | The effect of ghrelin is blocked by NPY antagonists, and by antibodies to NPY >and AgRP | 34 |
| 4 | In NPY or AgRP KO mice, the effect of ghrelin is reduced, in double KO is >completely abolished | 35 |
| 6 | Ghrelin activates orexin neurones | 36 |
| 6 | The effect of ghrelin is reduced by antibodies to orexin | 36 |
| 6 | The effect of ghrelin is reduced in orexin KO mice | 36 |