Separation and partial characterization of neuropeptide-inducing factors in heart cell conditioned medium

Various conditioned media contain multiple factors that regulate the expression of the neurotransmitters acetylcholine, serotonin, and catecholamines and the neuropeptides substance P, somatostatin, vasoactive intestinal polypeptide-related peptides, cholecystokinin, and enkephalins in cultured sympathetic neurons. Using biochemical and immunological methods, we identify at least three distinct factors in heart cell conditioned medium: one induces acetylcholine, substance P, somatostatin, and vasoactive intestinal polypeptide-related peptides while suppressing catecholamine expression, a second factor induces only vasoactive intestinal polypeptide-related peptides, and a third factor induces only somatostatin expression. These observations demonstrate the existence of a group of biochemically and immunologically distinct factors involved in phenotypic specification with unique, but partially overlapping activities. The analogy with the family of differentiation factors in the hematopoietic system is discussed.