Regulation by histamine of cAMP-dependent protein kinase in guinea-pig stomach

Abstract

The present investigation describes experimental conditions under which histamine stimulates cAMP-dependent protein kinase in the guinea-pig stomach. A histamine-responsive cAMP-dependent protein kinase was shown to be present in the soluble fraction obtained after a low speed centrifugation of the stomach homogenate. There was a small, but detectable stimulation of protein kinase activity and cAMP formation when tissue was incubated with histamine. This response to histamine was highly pronounced in the presence of a phosphodiesterase inhibitor. Protein kinase activation was assessed by measuring protein kinase activity ratio (activity -cAMP/+cAMP). Results indicate that protein kinase activity ratios reflect cAMP tissue levels. Binding of free cAMP by charcoal lowered both cAMP levels and protein kinase activity ratio, but histamine activation was still evident. Results suggest that only a portion of intracellular cAMP, probably in a bound form, is actually responsible for protein kinase activation, and the large accumulation of cAMP in the presence of a phosphodiesterase inhibitor probably does not reflect physiological levels.

Cyclic AMP and Gastric Secretion in Man: An in Vivo Study in Healthy Volunteers, Duodenal Ulcer Patients, and Pernicious Anaemia Patients

“…However, the total amount of cyclic AMP does not tell everything about its capacity to act as a second messenger and activate protein kinase. An earlier animal experiment suggests that only a portion of intracellular cyclic AMP, probably in a bound form, is actually responsible for protein kinase activation (28). Accordingly, the steady level of cyclic AMP in tissue homogenates after penta-gastrin injection does not rule out activation of a biologically important portion of cyclic AMP.…”