A novel synaptic transmission mediated by a PACAP-like neuropeptide in Drosophila.

Neuropeptide-mediated transmission was analyzed at Drosophila larval body-wall neuromuscular junctions. Focal application of vertebrate pituitary adenylyl cyclase-activating polypeptide (PACAP38) to the neuromuscular junction region triggered two temporally distinct muscle responses: an immediate depolarization followed by a large enhancement of K+ current. This late enhancement occurred many minutes after the early depolarization. High frequency stimulation of motor nerve fibers evoked a postsynaptic response mimicking that induced by PACAP38. This evoked response was desensitized by preincubation of the preparation with PACAP38. PACAP38-like immunoreactivity was also found in the Drosophila CNS and at almost all larval neuromuscular junctions. Moreover, an immunoreactive band that compares well with PACAP38 in size was identified in Western blot. These results demonstrate that a PACAP-like peptide may function in invertebrates and that a neuropeptide can evoke two distinct postsynaptic responses, each separated by up to 15 min. In addition, this initial electrophysiological study provides a basis for genetic analysis of neuropeptide function in Drosophila.