Vasoactive intestinal polypeptide (VIP)-sensitive adenylate cyclase in rat brain: regional distribution and localization on hypothalamic neurons.

The regional distribution of the vasoactive intestinal polypeptide (VIP)-sensitive stimulation of adenylate cyclase activity was studied in homogenates or rat brain. The order of sensitivity of this peptide on enzyme activity was: olfactory bulb > hippocampus > thalamus > occipital cortex congruent to frontal cortex congruent to midbrain congruent to hypothalamus > striatum > cerebellum congruent to brain stem > spinal cord. With neurotoxin-induced lesions the possible location of VIP-sensitive adenylate cyclase within the anterior hypothalamus was investigated. Intrahypothalamic 6-hydroxydopamine blocked the stimulatory effect of VIP on hypothalmic adenylate cyclase, but neither kainic acid nor 5,7-dihydroxytryptamine lesions had any effect. Similarly, there was a 71% reduction in the sensitivity of VIP-sensitive adenylate cyclase activity in animals whose hypothalamic noradrenergic innervation had been interrupted by transection of the ascending dorsal and ventral bundles. Biochemical analyses of the lesions suggested that loss of VIP action on adenylate cyclase was associated with loss of hypothalamic noradrenaline-containing neurons. These results may give insight into those regions of rat brain where VIP may have a neurotransmitter role, and point to a possible noradrenergic localization of the VIP-sensitive adenylate cyclase within the hypothalamus.