Altered adrenoceptor responsiveness during adrenaline infusion but not during mental stress: differences between receptor subtypes and tissues.
1. Effects of 3 h infusions of adrenaline (0.4 nmol kg-1 min-1) or placebo and of mental stress evoked by a colour word test (CWT) on adrenergic receptor function were investigated in healthy men. Responses of heart rate, blood pressure, plasma catecholamines, plasma cyclic AMP and plasma free fatty acids (FFA) were evaluated during infusions and CWT. In vitro beta 2-adrenoceptor numbers [( 125I]-HYP binding) and function (isoprenaline induced cyclic AMP accumulation) were studied on lymphocytes in all experiments. alpha 2-adrenoceptor binding [( 3H]-yohimbine and adrenaline) to intact platelets was evaluated in the infusion experiments only. 2. Placebo infusion evoked no major alterations of any parameter. 3. Adrenaline infusion raised venous plasma adrenaline levels to 4-5 nmol l-1, increased heart rate by 14 +/- 3 beats min-1 and plasma cyclic AMP by 17 +/- 3 nmol l-1, and decreased diastolic blood pressure by 15 +/- 5 mm Hg. These responses persisted throughout the infusion. Plasma FFA levels, on the other hand, increased at 30 min of infusion (from 236 +/- 44 to 717 +/- 92 mumol l-1) and returned to basal levels after 3 h of infusion. 4. In vitro, lymphocytes showed increased beta 2-responsiveness after 30 min of adrenaline infusion (delta cyclic AMP increased from 1.86 +/- 0.24 to 3.06 +/- 0.58 pmol/10(6) cells), but a decreased response (0.47 +/- 0.10 pmol/10(6) cells) after 3 h of infusion. [125I]-HYP binding to lymphocyte membranes showed a three-fold increase of Bmax at 30 min of adrenaline infusion followed by a return to basal values after 3 h of infusion. [125I]-HYP binding reflected the functional responsiveness of the lymphocytes in vitro poorly. alpha 2-adrenoceptors on platelets were not altered with regard to Bmax or Kd for [3H]-yohimbine binding or Ki for adrenaline displacement of [3H]-yohimbine binding. 5. CWT evoked marked circulatory changes, a four-fold increase in plasma adrenaline and a 60% increase in beta 2-adrenoceptor binding sites without changes in functional responsiveness of the lymphocytes. 6. We conclude that exposure to high physiological levels of adrenaline in vivo alters lymphocyte beta-adrenoceptor responsiveness in a biphasic manner, with an early increase followed by a later decrease, but that most beta-adrenoceptor mediated responses to adrenaline in vivo remain intact. Lymphocyte alterations may reflect recruitment of cells into the circulation during sympathoadrenal stimulation. Platelet alpha 2-adrenoceptors are apparently not easily subjected to agonist induced dynamic receptor regulation.(ABSTRACT TRUNCATED AT 400 WORDS)
Larsson
P T
PT
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Martinsson
A
A
Olsson
G
G
Hjemdahl
P
P
D000328:Adult; D001792:Blood Platelets / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000097:blood; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D007457:Iodine Radioisotopes; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism*
D007457:Iodine Radioisotopes; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D000242:Cyclic AMP; D007545:Isoproterenol; D004837:Epinephrine