Ontogeny of adenosine production and degradation and its implications in neonatal cerebral blood flow regulation.
Adenosine is a neuromodulator and potent vasoactive metabolite involved in various CNS regulatory mechanisms. We have recently shown that the newborn has maturationally related deficiency in adenosine production. The brains of Sprague-Dawley rats studied at ages 1, 7, 21 and 60 days (n = 6-12/group) showed that adenosine and its metabolites (measured by high-pressure liquid chromatography) is deficient in the newborn. Adenosine brain concentration was 0.99 nmol/g brain in newborn rats (day 0-1) and progressively increased postnatally to an adult value of 14.4 nmol/g brain. Inosine, a degradative product of adenosine by deaminase is significantly increased in newborns (mean +/- SEM = 48.3 +/- 14.3 nmol/g brain) relative to the 7-day-old rat (7.4 +/- 1.1 nmol/g brain) and to the adult (17.8 +/- 3.6 nmol/g brain). Thus, newborns have deficient adenosine brain concentration and this is due in part to increased deamination of adenosine. However, adenosine brain production may be augmented by ischemic-hypoxic insult. This was tested in 2 age groups of rats: 7 days old (n = 35) and adults (n = 35). Under nembutal anesthesia, bilateral carotid arteries were exposed and loosely tied, then both carotids were ligated and 5 animals from each group were decapitated and heads immediately frozen in liquid N2 at 5, 15, 30, 60, 120 and 300 s after ligation. Similar animals with carotids exposed but not ligated served as control (time zero). Brains were removed and assayed for adenosine and metabolites using high-pressure liquid chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)
Aranda
J V
JV
Developmental Pharmacology and Perinatal Research Unit, McGill University, Montreal Children's Hospital, P.Q., Canada.
Beharry
K
K
Laudignon
N
N
Sasyniuk
B I
BI
D000241:Adenosine / Q000096:biosynthesis* / Q000502:physiology; D000375:Aging / Q000378:metabolism* / Q000502:physiology; D002560:Cerebrovascular Circulation; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn / Q000378:metabolism* / Q000502:physiology
D000241:Adenosine