title: Activation of PAC(1)  and VPAC receptor subtypes elicits differential physiological responses from sympathetic preganglionic neurons in the anaesthetized rat.
abstract: OBJECTIVE
  Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuropeptide with central and peripheral cardiovascular actions. Intrathecal PACAP increases splanchnic sympathetic nerve activity and heart rate, but not mean arterial pressure (MAP). We hypothesize that the three PACAP receptors (PAC(1) , VPAC(1) and VPAC(2) ) have different actions in central cardiovascular control, and that their summed effect results in the lack of MAP response observed following intrathecal PACAP injection.
  
  
  METHODS
  The effects of the PACAP receptors on baseline cardiovascular parameters were investigated using selective agonists and antagonists administered into the intrathecal space of urethane-anaesthetized, vagotomized and artificially ventilated male Sprague-Dawley rats.
  
  
  RESULTS
  Selective activation of the PACAP receptors had different effects on MAP. When activated by maxadilan, PAC(1) receptors increased MAP. The VPAC receptors decreased MAP when both were activated with vasoactive intestinal polypeptide or when only VPAC(1) receptors were activated. The PAC(1) and VPAC(2) receptor antagonist PACAP(6-38) had no cardiovascular effects, suggesting that PACAP is not tonically released.
  
  
  CONCLUSIONS
  PACAP neurotransmission was not responsible for the moment-to-moment tonic regulation of central cardiovascular control mechanisms. Nevertheless, PACAP release within the spinal cord may have pleiotropic effects on sympathetic outflow depending on the postsynaptic receptor type. PAC(1) and VPAC receptor subtypes produced opposing changes in blood pressure when activated by intrathecal PACAP-38 in the anaesthetized Sprague-Dawley rat, resulting in no net change in MAP.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Inglott
authors.forename: Ethan A
authors.initials: EA
authors.lastname: Lerner
authors.forename: Paul M
authors.initials: PM
authors.lastname: Pilowsky
authors.forename: Melissa M J
authors.initials: MM
authors.lastname: Farnham
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000166:cytology
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide