Alpha-adrenergic receptor function in schizophrenia, affective disorders and some neurological diseases

Marian S. Kafka, Daniel P. van Kammen, Joel E. Kleinman, John I. Nurnberger, Larry J. Siever, Thomas W. Uhde, Ronald J. Polinsky

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44 Scopus citations

Abstract

Platelet α-adrenergic receptor function was assessed by correlating the number of α-receptors measured by the specific binding of an α-receptor antagonist, [3H]dihydroergocryptine ([3H]DHE), with an intracellular biological response, the inhibition of cyclic AMP (cAMP) production by an α-receptor agonist, norepinephrine (NE). Alpha-receptor function in adult control subjects of both sexes was compared with α-receptor function in patients with chronic schizophrenia and affective disorders. As a measurement of the specificity of α-receptor alterations in platelets from patients with schizophrenia or affective illness, platelet α-receptor function was compared in patients with other diseases in which adrenergic transmission may be altered, viz., essential hypertension, orthostatic hypotension, and Parkinson's disease. Finally, to provide a comparison group for studies of diseases of neural transmission in children, α-receptor function was measured in a group of young control males. The number of platelet α-receptors, relative to that in control subjects, was increased in patients with schizophrenia and affective illness. It was also elevated in patients with hypertension and idiopathic orthostatic hypotension (IOH), but not in patients with sympathotonic orthostatic hypotension (SOH), multiple system atrophy (MSA, Shy-Drager's Syndrome), or Parkinson's disease. When α-receptor function was compared in adult control subjects and young male controls, the number of α-receptors was similar in adult male, and young male, controls. Prostaglandin E1 (PGE1)-stimulated cAMP production in platelets was decreased in patients with schizophrenia. It was also lower in patients with hypertension and MSA, but unchanged in patients with affective illness, IOH, SOH, or Parkinson's disease. PGE1-stimulated cAMP production was similar in adult female, and young male, controls. In platelet lysates from schizophrenic patients the activity of the enzyme adenylate cyclase, which catalyzes the conversion of ATP to cAMP, was decreased. The decrease may be a major cause of decreased cAMP production in intact platelets from these patients. If the changes observed in platelets also occur in neurons, an increased number of α-receptors may play a role in the etiology of affective illness, while both an increase in the number of α-receptors and a decrease in cAMP production may play a part in the pathophysiology of schizophrenia.

Original languageEnglish (US)
Pages (from-to)477-486
Number of pages10
JournalCommunications In Psychopharmacology
Volume4
Issue number6
StatePublished - Dec 1 1980
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Kafka, M. S., van Kammen, D. P., Kleinman, J. E., Nurnberger, J. I., Siever, L. J., Uhde, T. W., & Polinsky, R. J. (1980). Alpha-adrenergic receptor function in schizophrenia, affective disorders and some neurological diseases. Communications In Psychopharmacology, 4(6), 477-486.