The Influence of Adrenoreceptor Activity on Crypt Cell Proliferation in the Rat Jejunum

Abstract

The influence of adrenergic stimulation, adrenergic blockade and sympathectomy on crypt cell cycle time and mitotic time in rat jejunum was studied. Alpha adrenergic stimulation by noradrenaline was found to shorten both cell cycle and mitotic times, whereas beta adrenergic stimulation by adrenaline or isoprenaline was found to prolong both cell cycle and mitotic times. Conversely, alpha adrenergic blockade by phentolamine prolonged cell cycle time and beta adrenergic blockade by propranolol or practolol shortened cell cycle time but not mitotic time. Both chemical and surgical sympathectomy inhibited crypt cell proliferation. Chemically sympathectomized animals manifested supersensitivity to exogenous noradrenaline.

Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth

“…It is not possible from the present experiments to determine whether the PG analogues are acting directly on the proliferating cells or indirectly through, for example, changes in blood supply, intestinal motility or mastcell activity. PG F2, has been shown to act, in some cases at least, by raising intracellular levels of cyclic guanosine monophosphate (cGMP) (Kuehl et al, 1973) and 3 other agents that have been shown to stimulate the formation of cGMP, namely noradrenaline (Schultz et al, 1975), acetylcholine (Goldberg et al, 1973) and serotonin (Goldberg et al, 1974), as well as dibutyryl cGMP itself, have been shown to accelerate jejunal-crypt cell proliferation (Tutton & Helme, 1974;Tutton, 1974Tutton, , 1977Tutton & Barkla, 1979b). However, in the case of colonic adenocarcinoma, whilst both serotonin (Tutton & Barkla, 1978b) and dibutyryl cGMP (Tutton & Barkla, 1979b) promote cell division, the PG F2, analogue inhibits both cell division and xenograft growth.…”

“…However, the response to a particular agent varies markedly between each of the tissues examined. For example, o-adrenoceptor agonists promote cell division in the jejunal and colonic epithelium but not in colonic adenocarcinomas (Tutton & Helme, 1974;Tutton & Barkla, 1977), whereas histamine and serotonin promote cell division in the jejunal crypts (Tutton, 1974 and in colonic tumours, but not in colonic crypts (Tutton & Barkla, 1978a, b). The (Druckrey et al, 1967;Tutton & Barkla, 1976).…”

“…Rats received a single injection of each drug at 12:00. Because PG F2a has been shown to increase noradrenaline output from some sympathetic nerve terminals (Kadowitz et al, 1972) and noradrenaline increased the mitotic rate in jejunal crypts (Tutton & Helme, 1974), the influence of 16,16-dimethyl PG F2a was also assessed in chemically sympathectomized rats. Twelve animals were injected i.v.…”

“…with 6-hydroxydopamine at a dose of 100 mg/kg, and 5 days later jejunal-crypt cell mitotic rates were measured with an without 16,16-dimethyl PG F2a. 6-Hydroxydopamine has previously been shown to cause destruction of sympathetic nerve terminals in rat jejunum (Tutton & Helme, 1974). 6-Hydroxydopamine was dissolved at a concentration of 100 mg/ml in distilled water containing sodium ascorbate at a concentration of 1 mg/ml.…”

Influence of biogenic amines on the growth of xenografted human colorectal carcinomas

“…IT IS NOW well recognized that biogenic amines are able to exert short-term influences, both excitatory and inhibiting, on cell proliferation in various malignant and non-malignant tissues (Bullough & Laurence, 1966;Byron, 1972Byron, , 1977Epifanova & Tchoumak, 1963;Hadden et al, 1970;Hunt & Tutton, 1976;Klein, 1977;Leeson & Voaden, 1970, Norrby, 1973Tutton, 1974Tutton, , 1976Tutton & Barkla, 1976, 1978aTutton & Helme, 1974). However, the influence of these ubiquitous agents on cell proliferation in human tumours and on volumetric changes in neoplasms does not appear to have been reported.…”