The regulation of airway caliber is important for supporting the physiological respiratory function and is con sidered to be mainly controlled by the central and peripheral nervous systems. In the present review, we discussed the resting tonus of the isolated airway smooth muscle of the guinea pig and compared it with that of the human; the former is similar to the latter because both are well-developed in the airway and well-responsive to a variety of mediators. The resting tonus of the isolated guinea pig trachea is largely decreased by indomethacin, a cyclooxygenase inhibitor, while that of the isolated human bronchus is increased following transient decrease by indomethacin. Furthermore, the human bronchus is markedly decreased by not only a selective peptide leukotriene antagonist, MCI-826, but also 5-lipoxygenase inhibitors, AA 861 and cirsiliol. These results indicate that contractile prostanoid(s) and peptide leukotrienes are possible mediators for the maintaining the resting tonus of the respective preparations. Both preparations still have a small but substantial part of the resting tonus resistant to these drugs, the mediator(s) responsible for which is not clarified yet. In short, arachidonate metabolites are major candidates for the resting tonus of either isolated guinea pig or human airway smooth muscle and may contribute to at least a part of the regulation of the airway caliber as autacoids in vivo.
Levodopa was released by depolarizing stimuli from rat striata in a transmitter-like manner in vitro and in vivo. Exogenous nanomolar levodopa stereoselectively facilitated the release of dopamine and noradrenaline via presynaptic β-adrenoceptors in brain slices even under inhibition of aromatic L-amino acid decarboxylase. This facilitation was competitively antagonized by levodopa methyl ester, whereas it was non-competitively antagonized by propranolol. Furthermore, picomolar levodopa stereoselectively potentiated the isoproterenol-induced facilitation of the noradrenaline release. Levodopa methyl ester selectively antagonized this potentiation, while propranolol antagonized both the facilitation by isoproterenol alone and its potentiation by levodopa. The recognition site for levodopa could be differentiated from the carrier proteins for levodopa transport, because nanomolar levodopa methyl ester abolished the levodopa-induced facilitation of the noradrenaline release, whereas a 30 times higher concentration of L-phenylalanine or L-leucine produced no antagonism. Microinjection of levodopa into the nucleus tractus solitarii led to dose-dependent decreases in arterial blood pressure and heart rate in rats in a levodopa methyl ester-sensitive manner. Based on these findings, we propose that levodopa itself is an endogenous neurotransmitter in the CNS.