IN-VITRO RECORDINGS FROM AREA POSTREMA NEURONS DEMONSTRATE RESPONSIVENESS TO ADRENOMEDULLIN

Adrenomedullin (ADM) is a recently discovered 52-amino acid peptide th at exerts potent vasodilatory effects in the periphery and influences the control of body fluid balance when injected centrally. In this stu dy extracellular single-unit recordings were obtained from 94 AP neuro ns in rat brain slices. Bath application of ADM (10(-7) M) excited 47% (32 of 68) of cells tested, and these effects were found to be dose d ependent from 10(-7) to 10(-9) M. Excitation was maintained during syn aptic blockade in. a low-Ca2+ artificial cerebrospinal fluid solution, demonstrating direct actions of ADM on these neurons. The remaining c ells were either unaffected (n = 25) or inhibited (n = 11) by ADM. ADM (10(-7) M) also influenced the spontaneous activity of 9 (7 inhibited , 2 excited) of 16 neurons located in the nucleus tractus solitarii (N TS). However, these effects could be eliminated during synaptic blocka de, suggesting indirect actions of the peptide on NTS neurons. These d ata demonstrate that a specific population of CNS neurons within the A P are directly influenced by ADM and suggest that ADM may exert its ef fects on the central control of fluid balance through direct actions a t this circumventricular organ.