Muscarinic M1, M3, Nicotinic,GABAA and GABAB Receptor ...

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Muscarinic M1 receptors are predominantly expressed in the forebrain, including the cerebral cortex, hippocampus and corpus striatum, where this subtype contributes by 50-60% to the total of the muscarinic receptors (Hamilton et al., 1997; Gerber et al., 2001; Miyakawa et al., 2001). The muscarinic M1 receptor subtype, which is also expressed in peripheral tissues, has been implicated in stress adaptive cardiovascular reflexes and central blood pressure control. Studies have shown that central administration of the muscarinic M1 specific antagonist pirenzepine lowered the blood pressure (Brezenoff & Xiao, 1986; Buccafusco, 1996). A putative overexpression of the M1 subtype in selected brain areas of spontaneously hypertensive rats has been reported (Scheucher et al., 1991). Muscarinic agonist depolarisation of rat isolated superior cervical ganglion is mediated through M1 receptors (Brown et al., 1980). Muscarinic M1 is one of the predominant muscarinic receptor subtypes expressed in pancreatic islets (Gilon & Henquin, 2001). Studies in pancreatic islets revealed that activation of muscarinic receptors is pertusis toxin insensitive and Gq mediated. Muscarinic M1 receptor number was decreased in the brainstem during pancreatic regeneration without any change in the affinity (Renuka et al., 2006). Muscarinic M2 receptor Muscarinic receptor activation in guinea pig heart produces a reduction in force of contraction and a decrease in the rate of beating. These effects are probably the consequence of inhibition of voltage-gated Ca 2+ channels and activation of inwardly rectifying K + channels, respectively. Extensive studies with many antagonists have defined this response as being mediated by the muscarinic M2 receptor (Caulfield, 1993). Muscarinic M2 receptors mediate both negative and positive ionotropic responses in the left atrium of the reserpinized rat, latter effect being insensitive to pertusis toxin (Kenakin & Boselli, 1990). Central cholinergic transmission is activated by inhibition of the presynaptic muscarinic M2 acetylcholine autoreceptor using selective antagonists. The presynaptic 25
26 Literature Review muscarinic M2 autoreceptor negatively influences the release of acetylcholine in several brain regions, including the striatum, hippocampus, and cerebral cortex (Kitaichi et al., 1999; Zhank et al., 2002). A direct consequence of brain muscarinic M2 autoreceptor inhibition is an elevation of acetylcholine release in the synaptic cleft. Methoctramine and other muscarinic M2 receptor antagonists have been shown to enhance the release of acetylcholine in different brain structures (Stillman et al., 1996). Muscarinic M3 receptor Muscarinic M3 receptors are broadly expressed in the brain, although the expression level is not high, compared to those of the muscarinic M1 and M2 receptors (Levey, 1993). Muscarinic M3 receptor is widely distributed in the peripheral autonomic organs with the highest expression found in the exocrine glands (Kashihara et al., 1992; Matsui et al., 2000). Expression of the muscarinic M3 receptor in the rat pancreatic islets and insulin secreting cell lines has been established (Lismaa et al., 2000). Muscarinic M3 receptor also triggers direct contractions of smooth muscle; however, it only represents a minor fraction of total muscarinic receptor population in smooth muscle. It is expressed in relatively low density throughout the brain. Studies using knock out mice for muscarinic M3 receptors gave evidences for the primary importance of these receptors in the peripheral cholinergic system. In urinary bladder, pupillary muscles and intestinal smooth muscles the cholinergic contractions are mediated predominately through muscarinic M3 receptors (Matsui et al., 2000). Muscarinic M4 receptor Muscarinic M4 receptor is known to be abundantly expressed in the striatum (Levey, 1993). Muscarinic M4 receptors act as inhibitory muscarinic autoreceptors in the mouse (Zhang & Warren, 2002). The neuroblastoma-glioma hybrid cell line NG108–15 expresses M4 mRNA and M4 receptors can be
Page 2: MUSCARINIC M1, M3, NICOTINIC, GABAA
Page 5 and 6: ACKNOWLEDGEMENT To the Almighty God
Page 7 and 8: Seema Chandran, Ms. Neema Ani Manga
Page 9 and 10: ABBREVIATIONS 5-HIAA 5 Hydroxy indo
Page 11 and 12: PFC Prefrontal cortex PLC Phospholi
Page 13 and 14: GABAC Receptors 34 Glutamic Acid De
Page 15 and 16: Behavioural response of control and
Page 17 and 18: the cerebral cortex of control and
Page 19 and 20: Muscarinic M1 receptor analysis Sca
Page 21 and 22: REAL TIME-PCR ANALYSIS 81 Real Time
Page 23 and 24: Real Time PCR analysis of GABAAα1
Page 25 and 26: pancreas of control and experimenta
Page 27 and 28: utilization is decreased in the bra
Page 29 and 30: impairment, coma or seizure (Cryer,
Page 31 and 32: achieving optimal blood sugar contr
Page 33 and 34: OBJECTIVES OF THE PRESENT STUDY 1.
Page 35 and 36: Literature Review Diabetes mellitus
Page 37 and 38: 12 Literature Review from the adren
Page 39 and 40: 14 Literature Review Hypoglycemic c
Page 41 and 42: 16 Literature Review respectively)
Page 43 and 44: 18 Literature Review in extracellul
Page 45 and 46: 20 Literature Review substrates in
Page 47 and 48: 22 Literature Review nucleus, altho
Page 49: 24 Literature Review al., 1990; Lev
Page 53 and 54: Signal transduction by muscarinic a
Page 55 and 56: 30 Literature Review nicotinic acet
Page 57 and 58: GABAA Receptors 32 Literature Revie
Page 59 and 60: 34 Literature Review GABAB-mediated
Page 61 and 62: 36 Literature Review (Erlander et a
Page 63 and 64: 38 Literature Review which could be
Page 65 and 66: 40 Literature Review administration
Page 67 and 68: 42 Literature Review the hippocampu
Page 69 and 70: 44 Literature Review understanding
Page 71 and 72: Confocal Dyes Rat primary antibody
Page 73 and 74: antipyryl)-p-benzo quinoneimine. Th
Page 75 and 76: was analyzed. Data was expressed as
Page 77 and 78: ANALYSIS OF THE RECEPTOR BINDING DA
Page 79 and 80: Taqman probes of muscarinic M1, M3,
Page 81 and 82: Taylor, 1968). The islets were isol
Page 83 and 84: Results BODY WEIGHT AND BLOOD GLUCO
Page 85 and 86: 60 Results IIH and C + IIH rats sho
Page 87 and 88: Real Time-PCR analysis of muscarini
Page 89 and 90: Real Time PCR analysis of SOD 64 Re
Page 91 and 92: 66 Results GABAAα1 receptor antibo
Page 93 and 94: 68 Results compared to diabetic gro
Page 95 and 96: 70 Results compared to diabetic rat
Page 97 and 98: 72 Results Muscarinic M3 receptor a
Page 99 and 100: Muscarinic M3 receptor analysis 74
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76 Results group, α7 nAChR mRNA si
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78 Results diabetic rats. In C + II
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Muscarinic M1 receptor analysis 80
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Real Time-PCR analysis of α7 nAChR
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Real Time PCR analysis of phospholi
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HIPPOCAMPUS Total muscarinic recept
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88 Results IIH and C + IIH group sh
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90 Results group, GLUT3 mRNA signif
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92 Results α7 nACh receptor antibo
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GABA receptor analysis 94 Results S
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96 Results control. D + IIH and C +
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Discussion Glucose is the principal
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100 Discussion The ability to sense
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102 Discussion The Y-maze test is a
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104 Discussion CHOLINERGIC ENZYME A
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106 Discussion Pancreas Insulin sec
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108 Discussion 2003). Cholinergic m
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110 Discussion brain for learning,
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112 Discussion hypoglycemia on brai
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114 Discussion shows impaired expre
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116 Discussion glycemic control is
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118 Discussion release (Ilcol et al
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120 Discussion al., 1992), it has t
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122 Discussion metabolic cycles are
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124 Discussion al., 1988). Low bloo
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126 Discussion modulate the second
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128 Discussion between excitation a
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130 Discussion hypoglycemic seizure
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132 Discussion Insulin secretion fr
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134 Discussion hyper and hypoglycem
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136 Discussion receptors in glucose
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138 Discussion exacerbated by recur
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140 Discussion Haces et al., 2010).
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142 Discussion hypoglycemic and dia
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144 Discussion transcription factor
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Summary 1. Insulin induced hypoglyc
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148 Summary specific antibodies con
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150 Summary 16. Transcription facto
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References Abdelmalik PA, Shannon P
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6. Anju T R, Pretty Mary Abraham, S
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Body weight (gm) 300 250 200 150 10
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Figure-3 Blood glucose levels at di
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Figure-5 Behavioural response of co
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Figure-7 Scatchard analysis of [ 3
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Figure-11 Real Time PCR amplificati
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C D + IIH Figure--25 Muscarinic M1
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Figure--27 α 7 nACh receptor expre
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Figure--47 Muscarinic M1 receptor e
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Figure--49 α7 nicotinic acetylchol
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Figure--71 α7 nicotinic acetylchol
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C Figure--93 GABAAα1 receptor expr
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Figure-101 Real Time PCR amplificat
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Figure—113 Muscarinic M3 receptor
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Figure--115 GABAAα1 receptor expre
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Figure-117 Scatchard analysis of [
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Figure-119 Scatchard analysis of [
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Figure-131 Muscarinic M1 receptor e
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C D + IIH Figure-133 GABAAα1 recep
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