Adrenoceptor Mediated Inhibition in the Rat Uterus

Ohia, Sunday Edet (1986) Adrenoceptor Mediated Inhibition in the Rat Uterus. PhD thesis, University of Glasgow.

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1. The rat uterus varies in its response to adrenoceptor agonists throughout the oestrous cycle, and the mechanisms underlying this variation have been investigated using pharmacological and biochemical techniques. 2. Acetylcholine (ACh) and potassium chloride (KCl) were used to raise tone in isolated uterine horn preparations. Both motor agents produced the highest tension in oestrus and this effect may reflect changes in thickness of the myometrium during the oestrous cycle. 3. The three adrenoceptor agonists studied, noradrenaline (NA), adrenaline (ADR) and salbutamol (SAL) produced inhibitory responses throughout the oestrous cycle. However, the maximum degree of inhibition achieved by each agonist varied in the four phases. 4. Stimulation of a-excitatory adrenoceptors contributed to the variation seen with NA and ADR (which possess a-adrenoceptor activity) but could not explain that of SAL, a selective P2-adrenoceptor agonist. 5. Blockade of agonist uptake processes into neuronal and extraneuronal sites, enhanced the inhibitory responses produced by NA, ADR and SAL, indicating a role for the removal mechanisms in the observed variation in response. 6. The variation in agonists responses persisted even when the contribution of both a-adrenoceptors and the uptake processes were controlled , suggesting that other factors could be involved. 7. Ovarian hormones appeared to play a major role in the variation since responses to NA, ADR and SAL were enhanced in uteri from ovariectomized rats. 8. Intramural, prostaglandin generation was involved in the responses to the adrenoceptor agonists, since cyclo-oxygenase inhibition, i. e., block of prostaglandin formation, enhanced the inhibition produced by NA, ADR and SAL. The effect was specific to the adrenoceptor agonists because the inhibitory responses to histamine and papaverine were unaffected by cyclo-oxygenase inhibition. 9. The leukotrienes are not involved in the adrenoceptor agonists responses, since inhibition of both cyclo-oxygenase and lipoxygenase produced effects similar to blocking the cyclo-oxygenase pathway alone. 10. Biochemical measurements of uterine adenosine 3',5' cyclic monophosphate (cAMP) were made throughout the oestrous cycle. Basal cAMP levels were similar in proestrus, oestrus, metoestrus and dioestrus. 11. cAMP did not appear to be involved in the variation in uterine response to adrenoceptor agonists because SAL-induced increases in cAMP levels were similar in all four phases of the oestrous cycle. Intramurally generated prostaglandins have no effect on cAMP formation, since cyclo-oxygenase inhibition was without effect on cAMP levels. 12. Calcium movements were studied in uteri from both intact and ovariectomized rats using radioactive calcium (45Ca2+). 45Ca2+ influx and efflux varied in the different hormonal conditions of the oestrous cycle, and in the absence of the hormones, following ovariectomy. 13. SAL had no effect on 45Ca2+ influx and efflux, indicating that the adrenoceptor agonists inhibitory responses in the rat uterus could involve an increased intracellular binding of calcium. 14. The variation in uterine response to the adrenoceptor agonists during the oestrous cycle is due, therefore, to the combined effects of a-adrenoceptor activity, agonist removal processes, intramurally generated prostaglandins and the ovarian hormones. Of these, the factors of major importance are the prostaglandins and the ovarian hormones.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Pharmacology
Date of Award: 1986
Depositing User: Enlighten Team
Unique ID: glathesis:1986-77328
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 09:12
Last Modified: 14 Jan 2020 09:12

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