Submitted on October 17, 2007
Accepted on February 11, 2008
PACAP is expressed in sympathoexcitatory bulbospinal C1 neurons of the brainstem and increases sympathetic nerve activity in vivo
Melissa Mary-Jean Farnham1, Qun Li1, Ann Kathleen Goodchild1, and Paul Martin Pilowsky2*
1 Sydney, New South Wales, Australia; Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia
2 Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia
* To whom correspondence should be addressed. E-mail: paul.pilowsky{at}mq.edu.au.
Pituitary adenylate cyclase activating polypeptide (PACAP) is an excitatory neuropeptide present in the rat brainstem. The extent of its localisation within catecholaminergic groups and bulbospinal sympathoexcitatory neurons is not established. Using immunohistochemical and in situ hybridisation, the extent of any colocalisation with catecholaminergic and/or bulbospinal projections from the brainstem was determined. PACAP mRNA was found in tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in the C1-C3 cell groups. In the RVLM, PACAP mRNA was found in 84% of the TH-ir neurons and 82% of bulbospinal TH-ir neurons. The functional significance of these PACAP mRNA positive bulbospinal neurons was tested by intrathecal administration of PACAP-38 in anaesthetised rats. Splanchnic sympathetic nerve activity doubled (110%) and heart rate (19%) rose significantly although blood pressure was unaffected. In addition, as previously reported, PACAP was found in the A1 cell group but not in the A5 cell group or in the locus coeruleus. The RVLM is the primary site responsible for the tonic and reflex control of blood pressure through the activity of bulbospinal presympathetic neurons, the majority of which contain TH. The results indicate 1) that ponto-medullary neurons containing both TH and PACAP that project to the intermediolateral cell column originate from C1-C3 and not A5, and 2) intrathecal PACAP-38 causes a prolonged, sympathoexcitatory effect.
