The acute actions of growth factors in smooth muscle systems.
Work over the past six to eight years has established that mitogenic polypeptides such as epidermal growth factor-urogastrone (EGF-URO) or platelet-derived growth factor (PDGF), commonly referred to as 'growth factors', can have rapid (seconds to minutes) regulatory actions in a variety of smooth muscle systems. With EGF-URO as a prototype example, this article describes three distinct smooth muscle response paradigms, two of which (type A and type B) comprise a rapid (seconds to minutes) increase in muscle tension) and one of which (type C) is characterized by an EGF-URO-mediated reduction in sensitivity to other agonists. The quite distinct signal transduction pathways for the three types of response paradigms are outlined, and the marked tissue and species variation in the types of smooth muscle responses that can be observed, even for a single growth factor agonist, are summarized. The article also illustrates that G-protein-coupled vasoactive agents such as angiotensin-II and vasopressin, which can act as 'growth factors' in cultured cell systems, can also work via tyrosine kinase pathways to cause contraction in some of the same intact smooth muscle preparations that contract in response to growth factors such as EGF-URO. Attention is drawn to the fact that many so-called 'growth factors', quite apart from stimulating cell division and differentiation, may in many instances act as rapid localized paracrine/autocrine regulators of tissues such as smooth muscle. It is also pointed out that some of the tyrosine kinase-modulated signal pathways usually associated with the mitogenic action of 'growth factors' may be involved not only in the rapid effects of agents such as EGF-URO in smooth muscle but also in the contractile actions of G-protein-linked agonists.
Hollenberg
M D
MD
Department of Pharmacology and Therapeutics, University of Calgary, Faculty of Medicine, Alberta, Canada.
D000818:Animals; D006133:Growth Substances / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D006133:Growth Substances