MATURATION OF CATECHOLAMINE RESPONSE AND EXTRANEURONAL UPTAKE IN RABBIT TRACHEA

The present study investigated whether maturational changes in extrane uronal catecholamine clearance accounted for the ontogenetic attenuati on of isoproterenol responsiveness in rabbit tracheal segments. Follow ing half-maximal contraction with acetylcholine (ACh) or KCl, tracheal ring segments (TS) isolated from newborn, 1-mo, and adult rabbits wer e relaxed with cumulative administration of isoproterenol. With postna tal maturation, there occurred a significant decrease in both maximal relaxation and sensitivity to isoproterenol in both ACh- and KCl-contr acted TS. Inhibition of extraneuronal catecholamine uptake with methyl prednisolone resulted in enhanced sensitivity to isoproterenol in 1-mo and adult, but not in newborn tracheal segments. In separate studies, extraneuronal catecholamine uptake was directly assayed in tracheal s egments isolated from rabbits of similar age and pretreated with neuro nal uptake and monoamine oxidase inhibitors. Maximal extraneuronal upt ake of [H-3]norepinephrine significantly decreased with age in trachea l tissues. In contrast, the sensitivity of the uptake process to norep inephrine increased with age. The relative catecholamine reserve marke dly decreased with age in rabbit tracheal segments and was directly re lated to the maximal degree of relaxation elicited with the P-adrenerg ic catecholamine, isoproterenol, in age-matched TS precontracted with either ACh or KCl. These findings suggest that, with maturation, extra neuronal uptake more effectively competes with beta-adrenoreceptor sti mulation and, accordingly, may contribute to the ontogenetic attenuati on of beta-adrenergic responsiveness in rabbit tracheal tissues.