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Effect of Melanotropic Peptides on Adenosine 3',5'- Monophosphate Accumulation by Regions of Rabbit Brain^*

DANIEL RUDMAN

Department of Medicine, Emory University School of Medicine Atlanta, Georgia 30322

Abstract

A previous study in the rabbit showed that intracisternal injection of the melanotropic peptides ACTH and β-MSH caused a 10- to 30-fold increase in concentration of cerebrospinal fluid cAMP within 30 min. The present investigation aimed to identify the region in the rabbit's brain where this increment of cAMP originated. Brain tissue was incubated for 5–20 min in Krebs-Ringer bicarbonate solution containing glucose and theophylline with or without specific dose of agonist, and the increment in cAMP in tissue plus medium was measured. We tested 18 brain regions in two groups: group I, six circumventricular organs: area postrema, subcommissural organ, pineal gland, and choroid plexuses of lateral, third, and fourth ventricles; group II, all other regions: brain stem, caudate nucleus, cerebellum, cerebral cortex, diencephalon, hippocampus, hypothalamus (anterior, mid, and posterior), medulla, midbrain and thalamus. The agonists were synthetic ACTH^1–24, synthetic -MSH, natur l β-MSH, and the bioactive amines histamine, norepinephrine, and serotonin. Agonists were tested initially at a concentration of 1000 µg/ml and, if active, at 10-fold dilutions to establish the minimal effective dose (MED). Results were as follows. In the 12 regions of group II, 9 responded to norepinephrine with an increase in cAMP level (MED, 6 x 10^-6 to 6 x 10^-5 M); in group I, only the pineal gland responded (MED, 6 x 10^-6 M). Histamine was active on all regions in group II (MED, 9 x 10^-7 to 9 x 10^-5 M) and on none in group I. Serotonin was active on 2 organs in group II (MED, 6 X 10^-5 M) and on none in group I. Contrastingly, the three melanotropic peptides stimulated cAMP accumulation in all 6 (ACTH) or in 5 of the 6 (-MSH and β-MSH) regions of group I (MED, 5 x 10^-8 to 2 x 10^-6 M). The melanotropic peptides did not stimulate cAMP accumulation in any region of group II.

These observations indicate the presence of an adenylate cyclase specifically responsive to melanotropic peptides in several circumventricular organs of the rabbit's brain.

Footnotes

^* This Work was supported by USPHS Grants AM- 13129 and RR-00039.

To whom requests for reprints should be addressed.

Received June 27, 1977.