Maturation of catecholamine response and extraneuronal uptake in rabbit trachea

The present study investigated whether maturational changes in extraneuronal catecholamine clearance accounted for the ontogenetic attenuation of isoproterenol responsiveness in rabbit tracheal segments. Following half-maximal contraction with acetylcholine (ACh) or KCl, tracheal ring segments (TS) isolated from newborn, 1-mo, and adult rabbits were relaxed with cumulative administration of isoproterenol. With postnatal maturation, there occurred a significant decrease in both maximal relaxation and sensitivity to isoproterenol in both ACh- and KCl-contracted TS. Inhibition of extraneuronal catecholamine uptake with methylprednisolone 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 segments isolated from rabbits of similar age and pretreated with neuronal uptake and monoamine oxidase inhibitors. Maximal extraneuronal uptake of [3H]norepinephrine significantly decreased with age in tracheal tissues. In contrast, the sensitivity of the uptake process to norepinephrine increased with age. The relative catecholamine reserve markedly decreased with age in rabbit tracheal segments and was directly related to the maximal degree of relaxation elicited with the beta-adrenergic catecholamine, isoproterenol, in age-matched TS precontracted with either ACh or KCl. These findings suggest that, with maturation, extraneuronal uptake more effectively competes with beta-adrenoreceptor stimulation and, accordingly, may contribute to the ontogenetic attenuation of beta-adrenergic responsiveness in rabbit tracheal tissues.

Ketamine: evidence of tissue specific inhibition of neuronal and extraneuronal catecholamine uptake processes

Ketamine (1.1 × 10−5 to 3.7 × 10−4 M) potentiated catecholamine responses of rat anococcygeus muscle and rabbit aorta in vitro. In the anococcygeus, potentiation was abolished by cocaine (2.9 × 10−5 M) pretreatment or by chemical sympathectomy using 6-hydroxydopamine (6-OHDA), but was unaffected by pretreatment with the extraneuronal uptake inhibitor cortisol (8.3 × 10−5 M), or the catechol-O-methyltransferase inhibitor tropolone (2.4 × 10−4 M). The action of ketamine mimicked the potentiating effect of cocaine on tyramine responses. In contrast, the potentiation by ketamine in rabbit aorta was unaffected by cocaine or 6-OHDA but was abolished by cortisol or tropolone; and ketamine potentiated tyramine responses, whereas cocaine inhibited them. Thus the mechanism of action by which ketamine produces potentiation of catecholamines in these two tissues is completely different. These results suggest that ketamine has the unusual ability to block neuronal and extraneuronal uptake and that the predominating mechanism will depend on the type of tissue examined and the morphology of its adrenergic innervation.