title: Excitatory action of pituitary adenylate cyclase activating polypeptide on rat sympathetic preganglionic neurons in vivo and in vitro.
abstract: In vivo and in vitro experiments were undertaken to evaluate the effects of pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) on rat sympathetic preganglionic neurons (SPNs). Intrathecal injection of PACAP-38 (0.1-1 nmol) via an implanted cannula to the T2-T3 segments of urethane-anesthetized adult rats caused a dose-dependent increase of mean arterial blood pressure from minutes to over 1 h. The pressor response was not antagonized by prior injection of the PACAP type II receptor antagonist PACAP6-38 (0.5 nmol), but was significantly attenuated by prior intravenous administration of phentolamine (1 mg/kg). As a positive control, intrathecal injection of glutamate (1 micromol) and substance P (SP, 5 nmol) caused a short- and long-lasting pressor response. Vasoactive intestinal polypeptide (VIP, 1 nmol) had no significant pressor effect. In the second series of experiments, whole-cell patch recordings were made from antidromically identified SPNs of immature (12-16-day-old) rat thoracolumbar spinal cord slices. Applied to the spinal cord slices by superfusion, PACAP-38 (10-30 nM) caused intense neuronal discharges with or without a long-lasting membrane depolarization. The depolarization was not prevented by superfusing the slices with tetrodotoxin (0.3 microM) or low Ca2+ (0.25 mM) solution, indicating that PACAP-38 directly depolarized the SPNs. The depolarization was insensitive to the type II PACAP receptor antagonist PACAP6-38. Collectively, these results provide evidence that PACAP-38 exerts a potent and long-lasting excitatory effect on SPNs, leading to an increase of spinal sympathetic outflow and one of the consequences of which is an elevation of blood pressure.
authors.affiliation: Department of Anatomy and Neurobiology, Medical College of Ohio, Toledo 43614, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Lai
authors.forename: S Y
authors.initials: SY
authors.lastname: Wu
authors.forename: H H
authors.initials: HH
authors.lastname: Lin
authors.forename: N J
authors.initials: NJ
authors.lastname: Dun
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
chemical_list: C495403:Adcyap1 protein, rat; D000959:Antihypertensive Agents; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D018698:Glutamic Acid; D010646:Phentolamine