Observations on the Cyclic Nucleotide Concentrations in Human Cerebrospinal Fluid

Abstract

Previous studies have shown that the concentrations of 3′,5′ cyclic adenosine monophosphate (cAMP) and 3′,5′ cyclic guanosine monophosphate (cGMP) in cerebrospinal fluid (CSF), brain, or both, are increased by melanotropic peptides and catechol amines, and by cholinergic agents. The present study measured the concentrations of cAMP, cGMP, and melanotropic activity in the CSF of normal patients and in 136 subjects with various neurologic diseases. In normal lumbar CSF, concentrations (ave ± SD) were: cAMP, 21 ± 8 mM; cGMP, 2.4 ± 0.5 mM; melanotropic activity, 17 ± 6 units/100 ml. Concentrations of cAMP, cGMP, and melanotropic activity did not differ significantly (P < .05) from normal in the following categories of adult and pediatric patients: back pain due to vertebral disease; seizures, headache or vertigo of unknown cause; cerebral atrophy; cerebral vascular disease; and brain tumor or subdural hematoma not causing increased ventricular pressure. Nine children with retarded psychomotor development caused by diffuse brain disease (infection, trauma, hemorrhage, degenerative process, long-standing hydrocephalus with thinning of the cerebral mantle) had subnormal levels of cAMP and melanotropic activity. These two variables were significantly correlated in the entire series of CSF samples (r = +0.55, P < .005). cGMP was elevated in the ventricular fluid of adult and pediatric patients when the ventricular pressure was abnormally elevated. The nucleotide's level rose as high as 50 × normal when ventricular pressure exceeded 300 mm H₂O. The concentration of ventricular cGMP was proportional to that of ventricular pressure (r = +0.76, P < .005). The correlation was similar regardless of the type of hydrocephalus (congenital or acquired, communicating or obstructive), the age of the patient, or the nature of the underlying disease.