Rats were injected daily with reserpine (2.5 mg/kg) for four days. The animals were sacrificed 4 hr subsequent to the last injection. Studies were performed as a means to determine alterations in catecholamine sensitivity of adenylate cyclase in the cerebral cortex following reserpine. In incubated tissue slices from reserpinized animals a greater accumulation of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in response to norepinephrine and isoproterenol was seen. In control animals both α-(phentolamine) and β-blocking agents (propranolol) inhibited norepinephrine-induced cyclic nucleotide accumulation, while in the reserpine-injected rats only propranolol was effective. The accumulation of cyclic AMP elicited by isoproterenol was inhibited by propranolol alone whether or not reserpine was administered. In cortical homogenates adenylate cyclase responsiveness to norepinephrine, isoproterenol and dopamine was enhanced in animals pretreated with reserpine. An identical observation was found in isolated neuronal fractions, although increased sensitivity of the enzyme to dopamine was now absent. Neither a- nor β-blocking agents were effective in broken cellular preparations. These data are interpreted to suggest that following depletion of catecholamines by reserpine, the β-receptor component of adenylate cyclase in the cortical neurones becomes hypersensitive to stimulation by catecholamines.
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