FIGURE 4-18 Cytoplasmic and nuclear signaling pathways of Vi vascular vasopressin receptors. Abbreviations: PLC, phospholipase C; PLD, phospholipase D; PLAz, phospholi-pase A2; PA, phosphatidic acid; AA, arachidonic acid; PC, phosphatidylcholine; PKC, protein kinase C; ER, endoplasmic reticulum; CO, cyclooxygenase pathway; EPO, epoxygenase pathway; IP3,1,4,5-inositol triphosphate; DAG, 1,2-diacylglycerol; Gq, G protein. Reproduced with permission from Thibonnier, M., Bayer, A.L., and Leng, Z. (1993). Regulatory Peptides 45, 79-84, 1993.

rat adrenal cortical cells in culture. Apparently, endogenous AVP may be released together with catecholamines during stress, and it may modulate steroidogenesis in the adrenal gland directly, in addition to the other better known humoral mechanisms leading to Cortisol release.

G. Behavioral Effects of VP

Lysine-and arginine-VP have been shown in model systems to positively affect the consolidation of memory and learning. Whereas puromycin induces amnesia, VP attenuates the puromycin effect by a process distinct from that by which puromycin exerts its effects on the cell. A single subcutaneous injection of VP increases resistance to the extinction of a pole-jumping avoidance response in the rat, confirming the positive effects of the hormone on conditioned behavior. So far, the structural requirements for the behavioral effects of VP are less stringent than those for hormonal activities (e.g., stimulation of renal adenylate cyclase activity). This suggests that the VP receptors in kidney and brain are different (Table 4-1). The Brattleboro rat has been used to assess the effects of VP deficiency. These animals are homozygous in their inability to synthesize VP, and they have diabetes insipidus. Other work suggests a single base deletion in the VP neurophysin gene that predicts a hormone precursor having a different C-terminus, indicating the possibility of faulty

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