Albumin protects against capsaicin- and adenosine-induced bronchoconstriction and reduces overflow of calcitonin gene-related peptide from guinea-pig lung.
In the guinea-pig isolated, perfused lung, the effect of albumin on oedema formation and bronchoconstriction as well as on capsaicin-induced overflow of calcitonin gene-related peptide-like (CGRP-LI) immunoreactivity has been examined. CGRP was used as an indicator of sensory nerve activation since it is more stable than the tachykinins substance P and neurokinin A. As expected, the lung water content was significantly (P less than 0.001) higher in lungs perfused with albumin-free buffer than when the buffer contained 4.5% albumin. Also, in albumin-free buffer the baseline airway resistance (RL) was increased and dynamic compliance (CDYN) reduced (P less than 0.001). Capsaicin (1 x 10(-6) M) was about 100 times less potent as a bronchoconstrictor when preincubated with albumin for 45 min, and the associated overflow of CGRP-LI was inhibited (from 221.0 +/- 63.4 fmol to 8 fmol fraction-1). When CGRP (50-200 pM) was incubated for 60 min with albumin, the recovery of CGRP-LI was 48% lower (P less than 0.01) than in the absence of albumin, corresponding to a loss rate of about 1% min-1. Catabolism or binding of neuropeptides can therefore hardly explain the diminished bronchoconstrictor potency of capsaicin. Capsaicin was also less effective as a constrictor in isolated bronchi after preincubation with albumin, suggesting that capsaicin itself may be bound or absorbed to this macromolecule. The bronchoconstrictor response to adenosine was also diminished in the presence of albumin. Adenosine was about 1000 times less potent as a bronchoconstrictor if dissolved in albumin 45 min before infusion, but only 10 times less potent when administered as bolus doses to albumin buffer-perfused lungs. Metabolism of adenosine may be the reason for the decreased potency of adenosine. The enzymatic activity may have been associated with impurities in the albumin preparation used (bovine serum albumin fraction V is greater than or equal to 96% pure) or contained in the protein itself. Since the bronchoconstrictor effect of acetylcholine was not reduced in the presence of albumin, it is not likely that albumin affects directly the contractility of the smooth muscle. These data demonstrate the importance of studying the influence of albumin on the in-vitro actions of pharmacological agents. The absence or presence of albumin products in nutrient buffer solutions may mean dramatic differences in potencies of certain drugs. Furthermore, bolus injections of agents are preferable, and preincubation together with albumin should be avoided.
Department of Clinical Pharmacology, University Hospital of Lund, Sweden.
F
F
Kröll
J A
JA
Karlsson
J M
JM
Lundberg
C G
CG
Persson
D000241:Adenosine; D000403:Airway Resistance; D000818:Animals; D001986:Bronchial Spasm / Q000139:chemically induced / Q000517:prevention & control*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin; D006168:Guinea Pigs; D007158:Immunologic Techniques; D008168:Lung / Q000033:anatomy & histology / Q000378:metabolism*; D008170:Lung Compliance; D008297:Male; D009929:Organ Size; D010477:Perfusion; D012709:Serum Albumin / Q000494:pharmacology*
D012709:Serum Albumin; D015740:Calcitonin Gene-Related Peptide; D000241:Adenosine; D002211:Capsaicin