Effects of the Acetylcholine, Bathanechol and Neostigmine on Isolated Intestinal Smooth Muscles - Assignment Example

Effects of the Acetylcholine (Ach), Bathanechol and Neostigmine on isolated Intestinal Smooth Muscles Student’s Name: Lecturer’s Name: Course: BMED 213 Date Submitted: Abstract The automatic nervous system, the entric nervous system, and the endocrine system modulate the gastric motility. It is through muscarinic receptors within the GIT smooth muscles that motility is stimulated. The amplification of contractility of smooth muscles is usually as a result of pharmacological agent’s neostigmine, an acetylcholinestrarase (AChE) and bethamechol, a cholinergic agonists inhibitor. In conducting analysis of differences in responses of ACh and ACh plus neostigmine, bethanechol and ACh, and, bethanechol plus neostigmine and bethanechol, a paired t test was undertaken to find a two tailed P value. This was through the use of the mean standard error of the mean of raw class data. The following were the results obtained from the mean contractile smooth muscle responses: ACh 1.17G, Bethanechol plus neostigmine 3.25g, ACh plus Neostigmine 1.86g, neostigmine -0.01g and bethanechol 3.09g. The comparisons of Bethanechol and ACh with two tailed P =< 0.0001. Comparisons of ACh plus Neostigmine and ACh, with two tailed P =< 0.01. Comparisons of Bethanechol plus neostigmine and Bethanechol, two tailed P => 0.05. The main aim of the experiment was to make a comparison of the differences and effects of bethanechol, Ach and Ach plus neostigmine, Ach and bethanechol, bethanechol plus neostigmine on contractibility of smooth muscle within the GI (gastrointestinal) tract. The experiment concluded that smooth muscles contraction is greatly amplified by bethanechol actions as compared to Ach. This is attributed by variation in structure in activation of AChE enzymatic activity. Furthermore, there are no stimulus effects by neostigmine on its own, however, it increases the ACh stimulation when they are combined making ACh increase its stimulus through inhibition of AChE actions. Combination of Neostigmine with bethanechol does not increase AChE stimulus. This is because AChE does not have bearing on actions of bethanechol. Introduction The autonomic nervous system, intrinsic entric nervous system, and the endocrine system modulate the gastric motility. Parasympathetic cholinergic neurons stimulate the motility activity while sympathetic nervous system inhibits it. It is through synapses which connect to the entric nervous system receptors cells where this is relayed as illustrated by Marieb & Hoehn (2010). It is through muscarinic receptors within the gastrointestinal tract smooth muscles that digestive contractions are stimulated. This is done by acetic acid and the neurotransmitter acetylcholine (ACh) (a choline ester). According to Sherwood (2010), SherwoodAcetylcholinesterase’s (AChE) enzymatic actions obstruct the build up of ACh in the synaptic cleft. This makes sure ACh stimulatory effects in absence of neural stimulation are stopped. Bethanechol is a cholinergic and parasympathetic agent that is associated to ACh in terms of structure. In the smooth muscle of urinary bladder and the gastrointestinal tract, bethanechol shows selectivity to muscarinic receptors stimulation. Unlike ACh, Bethanechol is not broken down by AChE (Marieb & Hoehn 2010). This usually leads to amplification of contractions by smooth muscles. Anticholinesterase agent neostigmine usually intensifies the contractions of smooth muscle. This is through binding to AChE that inhibits its ACh enzymatic breakdown allowing an accumulation that increases contractions. Pharmacological muscarinic antagonist atropine inhibits contraction of smooth muscles (Marieb & Hoehn 2010). The main action involves obstruction of postganglionic cholinergic nerve impulses transmission to the receptor cells. Aim The main aim of the experiment was to evaluate the differences and effects of bethanechol, ACh and ACh plus neostigmine, ACh and bethanechol, bethanechol plus neostigmine on contractibility of smooth muscle within the GI (gastrointestinal) tract. Method As per Laboratory protocol, pages 1-3, Isolated Intestinal Smooth Muscle Preparation, Bond University, 2011. Changes were made in the method: Atropine was not included among the drugs that were used in experiment to observe muscle contractile responses. Results Drug Added Mean Response (g) Standard Error of the Mean (g) ACh 1.17 0.22 Bethanechol 3.09 0.41 Neostigmine -0.01 0.04 ACh + Neostigmine 1.86 0.28 Bethanechol + Neostigmine 3.25 0.39 The table above shows the mean and standard error of response of GI tract after the addition of the drugs. The value of neostigmine is -0.01g. The differences in contractile response Ach plus Neostigmine and Ach is 0.69g. The difference in contractile response Bethanecol and Ach is 1.92g. The difference in contractile response of Bethanecol plus neostigmine and Bethanecol is 0.16g. A paired, two tailed P, t test on the instant program. Figure 1 shows the mean, standard error of the mean & comparisons of ACh plus Neostigmine and ACh; ACh and Bethanechol; and Bethanechol plus Neostigmine and Bethanechol. The comparisons of Bethanechol and ACh with two tailed P =< 0.0001 (0.0051). Comparisons of ACh plus Neostigmine and ACh, with two tailed P =< 0.01. Comparisons of Bethanechol plus neostigmine and Bethanechol, two tailed P => 0.05 (0.1740). Figure 2 A trace of smooth muscle contractions on pre and post drug added The figure above shows muscle contractions have different phases. There is a rise in the contraction of muscles after Bethanechol, ACh, Bethanechol plus Neostigmine and ACh plus Neostigmine were added. Discussion Smooth muscle contraction results in motility of the GI tract. This is only achieved when there is a short reflex arc of enteric nervous system and also when the endocrine system and autonomic nervous system have a long reflex arc. ACh which is a neurotransmitter stimulates gastric movement through muscarinic receptors. The action of ACh is terminated by Acetyl Cholinesterase (AChE) by breaking ACh into choline and acetic acid. This breakdown prevents a continued muscle fiber contraction. Bethanecol is a cholinergic and parasympathomimetic agent which is pharmacologically and structurally related to Acetylcholine (ACh) (Sherwood 2010, pp. 11). Bethanechol is however not inactivated by AChE but shows selectivity when stimulation of muscarinic receptors in the GI and urinary bladder occurs. The breakdown of ACh is inhibited when neogastigmine which is a pharmacological anticholinesterase binds to AChE. The result of these actions in relation to the activity of the smooth muscles is an accumulation of ACh. The ACh increases activity especially with an exaggerated stimulation which is also extended. Atropine can inhibit the contractions of the smooth muscles because of its muscarinic antagonist feature (Sherwood 2010, pp. 14). For inhibition of smooth muscles contractions to occur, there is blockage of transmission of postganglionic cholinergic nerve impulses to receptor cells. The table shows four groups out of five that displayed stimulus of smooth muscle contraction, Bethanechol, ACh, Bethanechol plus Neostigmine and ACh plus Neostigmine. Neostigmine exhibits that it does not have any stimulus on the smooth muscles when it is on its own with a response reading of 0.01gm. Figure 1 shows Figure 1 shows the mean, standard error of the mean & comparisons of ACh plus Neostigmine and ACh; ACh and Bethanechol; and Bethanechol plus Neostigmine and Bethanechol. ACH (1.17mg) and ACh plus Neostigmine (1.86mg) and both have a difference in mean response of 0.69mg. Bethanechol plus Neostigmine which weighed 3.25mg displayed an increase in response of 0.16mg when compared to Bethanechol (3.09 mg when it is on its own. The difference in values indicates that actions of neostigmine do not have any effect on bethanechol’s actions on the smooth muscles contractions. The differences of ACh (1.17gm) and Bethanechol (3.09gm) responses in muscle contraction show 1.92mg as its difference. With P =< 0.0001 indicates significant differences in the two values. The observation of the result is that Bethanechol is significantly higher in stimulus when added on smooth muscle hence causing a contraction as compared to ACh. The GI smooth muscle which is a single unit is stimulated using long reflex arcs of both the enteric and autonomic nervous system (Marieb & Hoehn 2010, pp. 22). Spontaneous phasic contractions were observed due to the drugs in figure 2. These contractions are due to short reflex of the pacemaker cells and enteric nervous system. Bethanechol is used in stimulating gastric motility, restore rhythmic peristalsis that is impaired and increase the tone of gastric smooth muscles. When obstruction is suspected, then Bethanechol should not be used. This drug is a cholinergic agonist mostly used in treating opioid-induced bowel dysfunction (Tamayo & Diaz-Zuluaga 2004). Opioids usually inhibit GI tract motility. Other contraindications include hyperthyroidism, bronchial asthma, peptic ulcer, epilepsy, coronary insufficiency, parkinsonism, hypotension and urinary infections (Campbell & Reece 2005, pp. 20). Conclusion Bethanechol as a cholinergic agonist amplifies the contraction of the smooth muscles as compared to ACh because of the differences in structure that inactivate AChE enzymatic activity. Neostigmine does not have any stimulus effects when it is on its own but when it is combined with ACh, it increases ACh stimulus by inhibiting actions of AChE. When Neostigmine is combined with bethanechol, it increases or amplifies AChE which does not have bearing on actions of Bethanechol. References Laboratory protocol, 2011, Isolated Intestinal Smooth Muscle Preparation, Bond University, pp. 1-3. Marieb, E.N. & Hoehn, K, 2010, Human Anatomy & Physiology.8th ed, Pearson Benjamin Cummings, pp. 23-26. Campbell, N. & Reece, J., 2005, Biology, 7th ed, Pearson Benjamin Cummings, San Francisco, pp. 1-30. Tamayo, A.C & Diaz-Zuluaga, P.A, 2004, ‘Management of opioid-induced bowel dysfunction in cancer patients’, Springerlink, vol.12, Viewed on 26th July 2011, Sherwood,L, 2010, Human Physiology: from Cells to Systems, 7th ed, Brooks/Cole, California, pp. 1-16. Read More