Effect of pH and lidocaine on beta-adrenergic receptor binding. Interaction during resuscitation?
Epinephrine and other beta-adrenergic receptor (beta AR) agonists are often administered during cardiopulmonary resuscitation, a time when acid-base abnormalities and arrhythmias also commonly occur. We tested whether beta 2AR binding is influenced by pH or the antiarrhythmic drug lidocaine, and whether pH might influence the interaction of lidocaine with beta 2ARs. With institutional review board approval and informed consent, 32 venous blood samples were obtained from volunteers. Lymphocytes (which bear beta 2ARs similar to those found in heart) were isolated by density gradient centrifugation. Specific binding of the beta AR ligand 3H-dihydroalprenolol (3H-DHA) was determined with lidocaine concentrations ranging from 10(-6) to 10(-2) mol/L (n = 18 experiments), and with and without lidocaine (n = 10 experiments), 100 mumol/L, and with and without QX314 (a permanently charged lidocaine derivative), 1 mmol/L (n = 4 experiments). Data are presented as percent of control-specific binding measured at a pH of 7.4. Statistical analysis consisted of Spearman's rank-test. 3H-DHA-specific binding increased (p < .001) with pH. Thus, alkaline conditions favored binding of 3H-DHA to the receptor. Lidocaine inhibited 3H-DHA binding to beta 2ARs in a concentration-dependent manner. The concentration that inhibited specific binding of 3H-DHA by 50% was 3.1 x 10(-4) mol/L (95% confidence limits, 1.3 x 10(-4) to 7.5 x 10(-4) mol/L). Lidocaine potency at inhibiting beta 2AR binding also increased with increasing pH; thus, there was limited benefit (in terms of increasing binding to beta 2ARs) to increasing pH when lidocaine was present. QX314, despite being present in a 10-fold greater concentration than lidocaine, had no effect on 3H-DHA binding at any tested pH. The affinity of beta 2 ARs for both 3H-DHA and lidocaine increased with pH. Thus, the response to beta 2AR agonists (when no lidocaine is present) might be expected to be greater with normal or alkalotic pH than under acidotic conditions, supporting the correction of metabolic acidosis to achieve optimal effects from beta 2AR agonists during resuscitation.
Modest
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VE
Department of Anesthesia, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1009, USA.
Butterworth
J F
JF
D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D016887:Cardiopulmonary Resuscitation; D004082:Dihydroalprenolol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008012:Lidocaine / Q000494:pharmacology*; D008214:Lymphocytes; D011446:Prospective Studies; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D008012:Lidocaine