Mechanisms of Inhibition and Contraction in Uterine Smooth Muscle

Al-Zadjali, Khamis Hussain (1988) Mechanisms of Inhibition and Contraction in Uterine Smooth Muscle. PhD thesis, University of Glasgow.

Abstract

(1) The possible mechanisms involved in the variation in rat uterine response to adrenoceptor agonists in preparations under different hormonal conditions have been investigated during the natural oestrous cycle and in pregnant and post-partum animals using pharmacological and biochemical techniques. (2) Uterine tone was induced with acetylcholine (Ach) in isolated preparations from non-pregnant and pregnant animals. Tension developed to Ach was more than twofold higher in uteri from 20-day and 1-day post-partum animals than in those from the four phases of the oestrous cycle. The observed variation in uterine response to Ach may reflect changes that occur in the thickness of the myometrium under the different hormonal states. (3) Noradrenaline (NA) , adrenaline (ADR), isoprenaline (ISO) and isoxsuprine (ISOX) produced inhibitory responses in uteri from non-pregnant and pregnant animals. During the oestrous cycle, the effects elicited by NA, ADR and SAL varied with the phase of the cycle. This variation could be partially due to the activation of a -excitatory receptors (NA and ADR) and/or to alterations in agonists removal mechanisms during the oestrous cycle. (4) Pre-treatment of animals with oestradiol- 17B increased the uterine response to SAL when compared to effects observed in natural oestrus indicating a role for the ovarian hormones in regulating adrenoceptor function in this preparation. (5) Inhibition of cyclo-oxygenase activity with flurbiprofen (FBF) enhanced uterine inhibitory response to the adrenoceptor agonists in preparations from nonpregnant, pregnant and post partum animals suggesting that intramurally generated prostaglandins were involved in their response. The effect elicited by FBF was, however, not reversed by excess exogenous arachidonic acid. Inhibition of phospholipase A2 activity with quinacrine also enhanced uterine inhibitory response to the adrenoceptor agonists. (6) Removal of the endometrium slightly reduced uterine response to ADR and SAL with the effects being greater in 1-day post-partum than in 20-day pregnant animals. In endometrium-free preparations, FBF had no significant effect on adrenoceptor agonists responses which would tend to suggest that the endometrium may play a role as a major source of PGs in the interaction between these agonists and the cyclo-oxygenase pathway leading to prostaglandin production. (7) Biochemical measurements of uterine adenosine 3',5' cyclic monophosphate (cAMP) were made in uteri from non-pregnant and pregnant animals. During the oestrous cycle, basal cAMP levels were similar in uteri from the four phases and cyclo-oxygenase inhibition with FBF had no effect on these levels nor on the ability of SAL to increase tissue cAMP content. Thus it would appear that cAMP may not be involved in the variation in uterine response to adrenoceptor agonists during the oestrous cycle. (8) Removal of the endometrium in uteri from 20-day pregnant animals did not alter basal tissue cAMP content neither did it affect the ability of SAL to increase cAMP levels. An effect on tissue cAMP metabolism may, therefore, not account for the observed changes in uterine response to adrenoceptor agonists in endometrium-free preparations. (9) In conclusion, presence of a heterogeneous population of adrenoceptors, an avid agonist removal mechanism, ovarian hormones and intramurally generated prostaglandins appear to contribute to the observed variations in uterine responses to adrenoceptor agonists during the oestrous cycle. cAMP is not the source of the variation. Adrenoceptor agonists effect on intramural prostaglandin production could play an important role in their overall response in the rat uterus since such an interaction was also present in preparations from pregnant and post-partum animals.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Pharmacology, Physiology, Endocrinology
• Date of Award: 1988
• Depositing User: Enlighten Team
• Unique ID: glathesis:1988-77792
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jan 2020 11:53
• Last Modified: 14 Jan 2020 11:53
• URI: https://theses.gla.ac.uk/id/eprint/77792