Biochemistry Objectives 44

1. Vasopressin:

a.  Gene coding and neurophysin II carrier: vasopressin is produced as preprovasopressin and subsequently cleaved into provasopressin (composed of vasopressin, neurophysin II, and a glycoprotein).

b.  Neurogenic and nephrogenic diabetes insipidus: both caused by a decreased response to ADH:

  1. Neurogenic (nonhereditary) diabetes insipidus: results from a problem in the neuronal pathway of vasopressin release. Can be caused by a problem in the supraoptic nucleus (defective preprovasopressin gene), blocked transit to the axon terminal, or blocked exocytosis.
  2. Nephrogenic (hereditary) diabetes insipidus: results from a problem in the nephron receptor response to vasopressin. Can be caused by a problem in V2 receptor sensitivity to ADH, aquaporin-2 channel production, or any point in the pathways converging to aquaporin integration into the apical membrane.

c.  Secretion control at the following levels:

  1. Physiological: secretion can be induced by three major mechanisms: increased plasma osmolarity sensed by osmoreceptors in the supraoptic nucleus, decreased volume sensed by volume receptors in the atrium, and decreased pressure sensed by baroreceptors in the carotid sinus/aortic arch.
  2. Biochemical: a neural impulse is given in response to physiological changes via acetylcholine. Acetylcholine increases intracellular Ca2+, and causes vesicles to release vasopressin and neurophysin II.

d.  Aquaporin-2 water channel regulation: vasopressin initiates Gs protein cascade ® cAMP ® PKA which phosphorylates aquaporin-2 channels. Phosphorylated aquaporin-2 channels integrate into the apical membrane to increase reabsorption of water in the distal nephron.

2. Hypothalamic releasing and inhibiting factors:

a.  TRH: acts on thyrotrophs to release TSH (Gq, IP3/DAG/Ca2+)

b.  GnRH: acts on gonadotrophs to release FSH and LH (Gq, IP3/DAG/Ca2+)

c.  CRH: acts on corticotrophs to release ACTH (Gs, increased cAMP)

d.  GHRH: acts on somatotrophs to release GH (Gs, increased cAMP)

e.  GHIH: acts on somatotrophs to inhibit GH release (Gi, decreased cAMP)

3. GnRH binding ® LH, FSH release: GnRH binds to a Gq protein linked receptor, causing an increase in PLC, Ca2+, and CaM-kinase. CaM-kinase phosphorylates enzymes, and in conjunction with Ca2+, induces FSH, and LH vesicles to fuse with the gonadotrope membrane.

4. Neuromodulator peptides induce desired behavior:

a. CCK-PZ: satiety (no more food needs to be eaten when CCK-PZ is secreted to digest food)

b.  GLP-1: suppresses appetite (causes insulin release, no more food needs to be eaten when glucose is already being stored)

c.  GnRH: mating behavior (increases LH and FSH, increased procreative capability)

d.  Oxytocin: maternal behavior (causes labor and milk ejection)

e.  Vasopressin: memory and learning (causes water reabsorption, and memory of place where water was so dehydration is avoided)