Effect of pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) on tissue oxygen content—Treatment in central nervous system of mice

• Published in: Regulatory peptides Vol. 123; no. 1-3; pp. 61 - 67
• Main Authors: Ohtaki, Hirokazu, Dohi, Kenji, Yofu, Sachiko, Nakamachi, Tomoya, Kudo, Yoshifumi, Endo, Sakura, Aruga, Tohru, Goto, Noboru, Watanabe, Jun, Kikuyama, Sakae, Shioda, Seiji
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Shannon Elsevier B.V 15-12-2004; Amsterdam Elsevier
• Subjects: Animals; Biological and medical sciences; Blood pressure; Blood Pressure - drug effects; Brain - drug effects; Brain - metabolism; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Brain Ischemia - physiopathology; Central Nervous System - drug effects; Central Nervous System - metabolism; Cerebral oxygen; Cerebrovascular Circulation - drug effects; Hypotension; Injections, Intravenous; Male; Medical sciences; Mice; Mice, Inbred BALB C; Nerve Growth Factors - administration & dosage; Nerve Growth Factors - pharmacology; Neuropeptides - administration & dosage; Neuropeptides - pharmacology; Neuropharmacology; Neuroprotective agent; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacology; Neurotransmitter Agents - administration & dosage; Neurotransmitter Agents - pharmacology; Oxygen Consumption - drug effects; Pharmacology. Drug treatments; Pituitary Adenylate Cyclase-Activating Polypeptide; Regional cerebral blood flow; Vasoactive Intestinal Peptide - administration & dosage; Vasoactive Intestinal Peptide - pharmacology; Vasoactive intestinal polypeptide; Vasodilation - drug effects; Blood pressure; Regional cerebral blood flow; Vasoactive intestinal polypeptide; Hypotension; Cerebral oxygen; Regional blood flow; Oxygen; Rodentia; Central nervous system; Oxygen content; Neuropeptide; Encephalon; Vertebrata; Mammalia; Mouse; Animal; Vasoactive intestinal peptide; Hemodynamics; Pituitary adenylate cyclase activating peptide
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/j.regpep.2004.05.013

It has been reported that pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in preventing neuronal cell death and is also a potent vasodilator. Cerebral hypotension and hypoperfusion during cerebral ischemia and neurodegenerative diseases are well known as some of the negative factors which aggravate neuronal cell death. Nevertheless, the effect of PACAP on the cerebral circulation was not understood well. Therefore, in the present study, we determined the mean arterial blood pressure (MBP), regional cerebral blood flow (rCBF) and cerebral oxygen content (pO2) in mice, and estimated the therapeutically useful doses of PACAP. Under barbiturate anesthesia, polyethylene tubes were inserted into mice to monitor MBP and to administer PACAP (5×10−13–5×10−8 mol/kg) or vasoactive intestinal peptide (VIP; 5×10−12 and 5×10−9 mol/kg). Then, MBP, rCBF and cerebral pO2 were simultaneously measured in the mice. PACAP (5×10−10–5×10−9 mol/kg) injections transiently decreased MBP, and cerebral pO2. PACAP (5×10−8 mol/kg) injections produced a long-lasting potent decline of MBP, rCBF and cerebral pO2. Therefore, PACAP should be applied at low doses which do not influence the MBP and cerebral circulation to determine the therapeutically useful doses of PACAP for neuroprotection.