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The β-Adrenoceptor-Blocking Drug Propranolol Prevents Secretion of Immunoreactive β-Endorphin and -Melanocyte-Stimulating Hormone in Response to Certain Stress Stimuli^*

Department of Pharmacology, Medical Faculty, Free University 1081 BT Amsterdam, The Netherlands

Address correspondence and requests for reprints to: F. J. H. Tilders, Department of Pharmacology, Medical Faculty, Free University, Van der Boechorstraut 7,1081 BT Amsterdam, The Netherlands.

Abstract

Handled female Wistar rats were exposed to one of the following stress stimuli: restraint, electric foot shocks, passive avoidance situation, ether, or nembutal anesthesia followed by ip formalin or laparotomy. Trunk blood was collected 2–4 min after initiation of the stress stimulus for the determination of immunoreactive β-endorphin (β-ENDi), ACTH (ACTHi), and -MSH (-MSHi). All stressors evoked a rapid increase of circulating β-ENDi to 0.75–2.10 ng/ml. All except passive avoidance situation also induced a rapid increase of plasma ACTHi to 0.45–0.70 ng/ml, whereas plasma a-MSHi increased after ether and restraint to 0.18–0.40 ng/ml but was not affected by formalin stress. To study the involvement of a β-adrenoceptor mechanism in stress-induced peptide secretion, rats were treated with D-propranolol or L-propranolol 40 min before stress exposure. Propranolol did not prevent the increase of plasma ACTHi to any of the stressors studied. L-Propranolol but not its inactive D-isomer reduced (restraint, passive avoidance) or abolished (electric foot shocks) the increase in plasma β-ENDi but did not affect the β-ENDi response to other stressors (ether, formalin, laparotomy). Similarly, L-propranolol attenuated the a-MSHi response to restraint but not to ether stress. To discriminate between corticotroph or melanotroph origin of β-ENDi released during stress, rats were treated with dexamethasone or were subjected to neurointermediate lobectomy (4 weeks). Neurointermediate lobectomy did not affect basal or stress-induced plasma ACTHi but resulted in undetectable -MSHi levels. It largely prevented the β-ENDi response to restraint stress (propranolol sensitive) but had little effect on the β-ENDi response to formalin stress (propranolol insensitive). Conversely, dexamethasone prevented stress-induced ACTHi response without affecting plasma -MSHi. The β-ENDi response to restraint stress (propranolol sensitive) was not changed but the response to formalin stress (propranolol insensitive) was largely prevented by dexamethasone. These results show that the intermediate lobe is the main source of β-ENDi secreted during exposure to stressors with a high emotional impact. Since intermediate lobe peptide secretion induced by such stimuli can be prevented by β-adrenoceptor blockade, we speculate that stress-induced discharge of catecholamines, possibly from the adrenal medulla, is the trigger signal for peptide secretion from the melanotrophs during this type of stress. (Endocrinology 115: 1051–1059, 1984)

Footnotes

^* This work was supported by Grant 13-25-29 of the Netherlands Foundation for Medical Research (FUNGO).

Received April 14, 1983.

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