Pulmonary surfactant, a mixture consisting of phospholipids (PL) and protei
ns, is secreted by type II cells in the lungs of all air-breathing vertebra
tes. Virtually nothing is known about the factors that control the secretio
n of pulmonary surfactant in nonmammalian vertebrates. With the use of type
II cell cultures from Australian lungfish, North American bullfrogs, and f
at-tailed dunnarts, we describe the autonomic regulation of surfactant secr
etion among the vertebrates. ACh, but not epinephrine (Epi), stimulated tot
al PL and disaturated PL (DSP) secretion from type II cells isolated from A
ustralian lungfish. Both Epi and ACh stimulated PL and DSP secretion from t
ype II cells of bullfrogs and fat-tailed dunnarts. Neither Epi nor ACh affe
cted the secretion of cholesterol from type II cell cultures of bullfrogs o
r dunnarts. Pulmonary surfactant secretion may be predominantly controlled
by the autonomic nervous system in nonmammalian vertebrates. The parasympat
hetic nervous system may predominate at lower body temperatures, stimulatin
g surfactant secretion without elevating metabolic rate. Adrenergic influen
ces on the surfactant system may have developed subsequent to the radiation
of the tetrapods. Furthermore, ventilatory influences on the surfactant sy
stem may have arisen at the time of the evolution of the mammalian bronchoa
lveolar lung. Further studies using other carefully chosen species from eac
h of the vertebrate groups are required to confirm this hypothesis.