Actions and interactions of colchicine and cytochalasin B on contraction of granulation tissue and on mitosis

Abstract

IT has been shown by Majno et al.¹ that a strip of growing granulation tissue (GT) cut from the wall of a 2- to 4-week-old granuloma pouch² or from the base of an open wound in the rat, contracts in vitro in response to 10⁷–10⁶ concentrations of 5-hydroxytryptamine, angiotensin and other agonists. An association between this pharmacological reactivity of GT and the phenomenon of wound contraction has been proposed¹ on the bases that the forces which cause a wound to contract are cellular in origin and generated by GT cells^3,4, and that fibroblasts proliferating in vitro and in vivo develop a muscle-like cytoarchitecture characterised by an increase in the number of microfilaments⁵. Also fibroblasts in culture contain abundant microtubules⁶ which can be rapidly destroyed by poisons such as colchicine^6–8 that prevent polymerisation of the tubular protein. For example colchicine can prevent microtubules comprising the mitotic spindle from forming and thereby inhibit karyokinesis (separation of chromosomes)⁹. The drug seems not to affect the functions of microfilaments, on which various types of contractile activity, including cytokinesis, depend¹⁰; the microfilaments are specifically inhibited by the drug cytochalasin B (ref. 11).