This set of Molecular Endocrinology Multiple Choice Questions & Answers (MCQs) focuses on “G Protein-Coupled Receptor Interactions”.
1. Which among the following is an example of a drug targeting GPCRs, which act as positive allosteric modulators of the calcium sensing receptor?
a) Calcimimetic drugs
b) Lipolic drugs
c) Agonic drugs
d) Drenching drugs
View Answer
Explanation: Drugs targeting GPCRs may act as agonists, antagonists or allosteric modulators. For example, by binding to the seven transmembrane domain and acting as positive allosteric modulators of the calcium sensing receptor, calcimimetic drugs inhibit the PTH release.
2. Which among the following couple of orphan GPCRs are activated by succinate and α-ketoglutarate?
a) GPR78, GPR79
b) GPR91, GPR99
c) GPR71, GPR79
d) GPR81, GPR89
View Answer
Explanation: The physiologically relevant activators of the orphan GPCRs, GPR91, and GPR99, respectively, were shown to be the Krebs cycle intermediates, succinate and alpha-ketoglutarate. They regulate renin release and blood pressure through binding.
3. Which among the following is an example of a disease caused by G Protein–coupled LH receptor’s gain-of-function mutations?
a) Familial nonautoimmune hyperthyroidism
b) Sporadic hyper functional thyroid nodules
c) Familial male precocious puberty
d) Familial hypocalcemic hypercalciuria
View Answer
Explanation: Familial male precocious puberty is the disease caused by G Protein–coupled LH receptor’s gain-of-function mutations. In most cases, clinically significant signal transduction impairment requires the loss of both GPCR gene alleles, most of which are inherited in an autosomal recessive fashion.
4. GPCRs are a major target for drug development.
a) True
b) False
View Answer
Explanation: GPCRs have been a major target for drug development because of their diverse and critical roles in normal physiology, their cell surface accessibility, and their ability to synthesise selective agonists and antagonists. One estimate is that about 65% of prescription medicines are targeted by GPCRs.
5. A much greater diversity of receptor subclasses became apparent with the cloning of GPCR cDNAs.
a) True
b) False
View Answer
Explanation: With the cloning of GPCR cDNAs, on the basis of pharmacological studies, a much greater diversity of receptor subclasses became apparent than expected. Five muscarinic receptor subtypes and an even larger number of serotoninergic GPCRs have been identified like this.
6. Which among the following defect on TSH receptor can cause a form of hypothyroidism that mimics TSH deficiency?
a) TSH receptor gain-of-function mutations
b) TSH receptor loss-of-function mutations
c) TSH receptor degeneracy
d) TSH receptor inherited disorder
View Answer
Explanation: Most illnesses manifest as resistance to the normal agonist’s action and resemble the agonist’s deficiency. For instance, loss-of-function mutations in the TSH receptor cause a type of hypothyroidism that mimics TSH deficiency.
7. Which disease is caused by loss-of-function mutations of the GnRH receptor, the orphan GPR54, or the prokineticin receptor 2 (PROKR2)?
a) Hypogonadotropic hypogonadism
b) Familial male precocious puberty
c) Familial hypocalcemic hypercalciuria
d) Familial male precocious puberty
View Answer
Explanation: Loss-of-function mutations of the GnRH receptor, orphan GPR54, or prokineticin receptor 2 can cause hypogonadotropic hypogonadism. In the first case, resistance to the action of GnRH can happen.
8. Nephrogenic diabetes insipidus (renal vasopressin resistance) is caused by loss-of-function mutations in which of the following genes?
a) Chemokine Receptor 8 (CKR8)
b) Leptin Receptor 7 (LR7)
c) Prokineticin receptor 2 (PROKR2)
d) Arginine vasopressin receptor 2 gene (AVPR2)
View Answer
Explanation: Nephrogenic diabetes insipidus (i.e., resistance to renal vasopressin) is caused by loss of function mutations found on the X chromosome in the arginine vasopressin receptor 2 (AVPR2) gene. When they inherit a mutated gene, males with a single copy of the gene develop the disorder.
9. Which among the following is an exception to the association between GPCR loss-of-function mutations and hormone resistance?
a) Extracellular Ca2+-sensing receptor
b) Intracellular Ca2+-sensing receptor
c) Extracellular Cl-sensing receptor
d) Intracellular Cl-sensing receptor
View Answer
Explanation: An interesting exception to the association between GPCR loss-of-function mutations and hormone resistance is the extracellular Ca2+-sensing receptor. This receptor’s loss of-function mutations mimic a state of hormone hypersecretion.
10. Which type of mutation is seen in GPCR gain of functional mutations?
a) Nonsense
b) Missense
c) Frameshift
d) Point
View Answer
Explanation: Missense, nonsense, or frameshift mutations that truncate the normal receptor protein are loss-of-function mutations. GPCR mutations for gain-of-function are almost always missense mutations.
11. Activating missense mutations in which among the following genes lead to the syndrome of nephrogenic inappropriate antidiuresis?
a) AVPR2 of arginine 137
b) AVPR3 of lysine 128
c) CVGR of arginine 98
d) SNRP of lysine 198
View Answer
Explanation: Activation of arginine 137 missense mutations in AVPR2 leads to the nephrogenic syndrome of inadequate antidiuresis. This is part of the DRY motif retained in most Family 1 GPCRs at the intracellular boundary of transmembrane helix 3.
12. Which among the following is an exception to the mutation of GPCRs in which there is no clinically mimicked states of agonist excess?
a) Calcium sensing receptor
b) Phosphate sensing receptor
c) Sodium sensing receptor
d) Potassium sensing receptor
View Answer
Explanation: Diseases induced by activating GPCR mutations resemble agonist excess states clinically, but direct measurement reveals that the concentrations of agonists are poor, indicating natural mechanisms of negative feedback. An important exception is the Ca2+-sensing receptor.
13. A loss-of-function mutation in the hypocretin (orexin) type 2 receptor gene was identified in which of the following diseases?
a) Canine Narcolepsy
b) Albino neoplasm
c) Ascites lymphoma
d) Lectic lymphoma
View Answer
Explanation: In canine narcolepsy, a loss-of-function mutation was identified in the hypocretin (orexin) type 2 receptor gene. Dozens of knockout models of the mouse GPCR gene have been created, and many of them have reported interesting and unexpected phenotypes.
14. Disruption of the PTH/PTH-related protein receptor gene causes which disease in humans?
a) Blomstrand chondrodysplasia
b) Phenylketonuria
c) Maple Syrup Urine Disease
d) Ascites Lymphoma
View Answer
Explanation: Disruption of the protein receptor gene linked to PTH/PTH causes the human condition known as Blomstrand chondrodysplasia. This also impairs the natural development and growth of bones in mice.
15. Which among the following molecules were shown to rescue expression and function in mice with nephrogenic diabetes insipidus caused by a nonsense mutation in AVPR2 gene?
a) Aminoglycosides
b) Tetra glycosides
c) Peptidoglycans
d) Glutathione
View Answer
Explanation: Aminoglycosides inhibit premature termination codons. In mice with nephrogenic diabetes insipidus caused by a nonsense mutant in AVPR2, these molecules have been shown to rescue expression and function.
Sanfoundry Global Education & Learning Series – Molecular Endocrinology.
To practice all areas of Molecular Endocrinology, here is complete set of 1000+ Multiple Choice Questions and Answers.
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