Journal Article•
Cyclic adenosine 3',5'-monophosphate formation in brain slices: stimulation by batrachotoxin, ouabain, veratridine, and potassium ions.
TL;DR: The results suggest a relationship among depolarization, transmitter release, and cyclic 39,59-AMP formation in brain.
Abstract: The formation of cyclic adenosine 39,59-monophosphate- 14 C from endogenous ATP- 14 C is greatly stimulated on incubation of cerebral cortex slices with depolarizing agents such as batrachotoxin, veratridine, ouabain, and potassium ion. In slices of cerebral cortex, batrachotoxin is the most potent known stimulant (ED 50 = 1 x 10 -7 M) of cyclic 39,59-AMP- 14 C formation. Stimulation of cyclic 39,59-AMP- 14 C formation by depolarizing agents requires calcium ions and is inhibited by theophylline. Stimulation of cyclic 39,59-AMP- 14 C formation by histamine, in contrast, does not require calcium ions and is not inhibited by theophylline. The results suggest a relationship among depolarization, transmitter release, and cyclic 39,59-AMP formation in brain.
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TL;DR: It was concluded that the residual activity associated with the purified enzyme was due to an incomplete removal of the activator from the enzyme.
501 citations
TL;DR: Sutherland et al. as mentioned in this paper showed that cyclic AMP functioned as an intracellular second messenger, synthesized in response to certain hormones and which, by activating the appropriate sequence of enzymes, produced the specific biologic response of the target cell to the hormone.
Abstract: Less than two decades ago Sutherland and Rall (1958; Rall et al., 1957) discovered a heat stable factor now known as adenosine 3′,5′-monophosphate, which accumulated in particulate fractions of liver homogenates exposed to epinephrine. This factor activated the breakdown of glycogen by soluble cytoplasmic enzymes. Although epinephrine activates glycogenolysis in intact hepatocytes, the hormone has no such effect on the soluble enzymes. Sutherland and Rall (1960; Rall and Sutherland, 1958, 1961, 1962) proposed that epinephrine might trigger the glycogenolytic response of hepatocytes by activating the synthesis of this nucleotide (cyclic AMP) whose structure (Fig. 1) by then had been shown to contain a unique cyclic phosphate bond (Lipkin et al., 1959). The polypeptide hormone glucagon also triggers the glycogenolytic response of liver, and activates the synthesis of cyclic AMP. From these and related observations on the actions of other hormones, the concept arose that cyclic AMP functioned as an intracellular “second messenger”, synthesized in response to certain hormones and which, by activating the appropriate sequence of enzymes, produced the specific biologic response of the target cell to the hormone (Sutherland et al., 1965).
229 citations
TL;DR: The subsequent effects of this increase in Na+ permeability evoked by batrachotoxin—such as membrane depolarization, enhanced spontaneous transmitter release, muscle contracture, and enhanced formation of cyclic AMP in brain slices—may be blocked reversibly by tetrodotoxin.
Abstract: Batrachotoxin has been shown to be a pyrrolecarboxylic ester of a novel steroidal base with unique and selective actions on a variety of electrogenic membranes. The effects of batrachotoxin in neuromuscular preparations both pre- and postsynaptically, in nerve axons, in superior cervical ganglion, in heart Purkinje fibers, and in brain slices appear to be due to the selective and irreversible increase in permeability of membranes to sodium ions. The subsequent effects of this increase in Na(+) permeability evoked by batrachotoxin-such as membrane depolarization, enhanced spontaneous transmitter release, muscle contracture, and enhanced formation of cyclic AMP in brain slices-may be blocked reversibly by tetrodotoxin.
194 citations
TL;DR: The results suggest a role for adenosine in responses to most agents in brain slices and indicate that 2′-deoxyadenosine may be a more specific adenoine antagonist than either methylxanthines or adenosines deaminase.
144 citations
TL;DR: The data provide no evidence for the presence of more than one major compartment of adenine nucleotides in brain slices that can serve as a source of nucleotide precursor for cyclic AMP.
136 citations