catecholamiens

Question 2

cortex develops from _____;invades retroperitoneal mesenchyme about week 5medulla derived from ___ ____;about week 7 of development

Answer 2

1. mesothelium2. neural crest

Question 3

PNMT is activated by_____ and ____

Answer 3

sympathetic nerves and glucocorticoids

Question 4

cholinergic innervation from the ___nerve stimulates exocytosis from chromaffin granules–> release catecholamines

Answer 4

1. splanchnic

Question 5

?% adrenaline?% noradrenalineany one cell secretes either adrenaline OR noradrenaline

Answer 5

1. 802. 20In most cells, granules contain PNMT and noradrenaline is methylated to adrenaline

Question 6

β -adrenoceptor activates ___–>____ cAMPα1-adrenoceptor activates ____–> ↑ ____ and ____α2-adrenoceptor activates ____ –> ____ in ____

Answer 6

1. Gαs , increase2. Gαq –> IP3 and DAG3. Gαi. decrease in cAMP

Question 7

Binding to β2 adrenoceptorsAdrenaline is bound to amino acid sidechains in helices ___, ___ and __Conformational change in thereceptor when adrenaline binds

Answer 7

3, 5 and 7

Question 8

What receptors are involved in ↑ :…. glycogenolysis  lipolysis  gluconeogenesis  secretion of insulin and glucagon  heart rate

Answer 8

1. β22. β33. α14.β25.β1

Question 9

What receptors are involved in ↑ :…. contractility of heart muscle  arteriolar tone in non-muscle vascular beds, leading to vasoconstriction and elevated BP  tone in gastro-intestinal sphincters  tone in bronchial smooth muscle

Answer 9

1. β1 2. α13. α14. α1

Question 10

What receptors are involved in decreased…. arteriolar tone in skeletal muscle  tone in non-sphincter muscles of GI tract tone in bronchial smooth muscle – bronchodilation  tone in non-sphincter smooth muscles

Answer 10

1. β2 2. β13. β24. α1

Question 11

Continuous exposure to adrenaline ________multiple GPCRs___phosphorylates several serine and threonine residues in the cytosolic domain of ALL GPCRs,

Answer 11

1. desensitises 2. PKA Heterologous desensitisation: cell loses the ability to respond to multiple stimuli acting through different Rs and the samesignalling pathwayhomologous desens: β Rs

Question 12

Prolonged activation : receptor stimulates b-adrenoceptor kinase (bARK) this phosphorylates Ser and Thr residues in C-terminal and ___intracellular loop conformational change allows it to bind __ which blocks binding of G-protein

Answer 12

1. third2. β-arrestin,β-Arrestin binds clathrin (and other proteins), –> endocytosis and internalisation of the receptor

Question 13

rarely, following adrenalectomy or destruction by haemorrhage,replacement of the ____hormones is essential, and is sufficient to maintain BP and glucose homeostasis w/o replacing the adrenal medullary hormones

Answer 13

1. adrenocortical (steroid)

Question 14

PhaeochromocytomaImmediate management:α antagonist (e.g. )β antagonist (e.g. )Scan using radioactive compound (MIBG), taken up by catecholamine-producing tissues

Answer 14

1. phenoxybenzamine2. propranolol

Question 15

Catecholamines are rapidly clearedand catabolised by: methylation: ________ oxidation: ____ and _______ _______

Answer 15

1. COMT2. MAO and aldehyde dehydrogenase

Question 16

β adrenoceptor has a very ___ extracellular N-terminus, inadequate to be a LBD.Instead, 7 membrane helices from ____binding pocket

Answer 16

1. short2. hydrophilic

Question 17

Actions of catecholamines________ ↑ both systolic and diastolic BP ______ only ↑ systolic BP and ↓ diastolic BP –> no change in mean BP _____decreases gutmotility and can act as a bronchodilator. Effects of ____on gut motility less marked and no effect on bronchial tone.catecholamines ↑ glycogenolysis (mainly ___) and the plasma [ NEFA ] (mainly ___)

Answer 17

1. Noradrenaline2. Adrenaline3. Adrenaline 4. Noradrenaline5.adrenaline6. noradrenaline Both can dilate the pupil (if applied at high concentrations) and induce piloerection.

Question 18

Multiple Endocrine Neoplasia – MEN type IAlmost all patients develop parathyroid tumours –> _______parathyroidectomy: remove 3½ of 4 ~40% develop pancreatic tumours____–> excessive gastric acid secretion, ulceration40 – 60% develop anterior pituitary tumoursprolactinoma, familial acromegaly

Answer 18

1. hypercalcaemia2. gastrinoma

Question 19

Multiple Endocrine Neoplasia – MEN type Irarely, develop tumours of: adrenal cortex (commonly benign)carcinoid tumours of ____, ___-, or ___neuroendocrine tumours; ~10% develop carcinoid syndrome: (5)secretion of 5HT, prostaglandins, kinins, gastrin, etcDiagnosis ?

Answer 19

1. thymus, lung or stomach2. flushing, diarrhoea, palpitations, hypotension, right-sided heart disease3. family history and tumoursin 2 of: parathyroid, pancreatic islets, anterior pituitary

Question 20

Multiple Endocrine Neoplasia – MEN type Iloss of function mutations in the MEN gene, which codes for __Menin is a nuclear, tumour suppressor protein: regulation of transcription  genome stability cell differentiation and proliferation

Answer 20

1. meninMenin also interacts with TGF-β signalling at the level of SMAD

Question 21

How can a loss of function mutation have autosomal dominant inheritance?

Answer 21

a) a somatic mutation occurs in the normal allele, –>2 defective allelesb) inactivation of the normal allele

Question 22

Multiple Endocrine Neoplasia – MEN type IIMEN IIa (~__% of MEN II) medullary thyroid carcinoma very aggressive; early ____required phaeochromocytoma (bilateral) parathyroid hyperplasia

Answer 22

1. 95 2. thyroidectomy

Question 23

MEN IIb (~___% of MEN II) medullary thyroid carcinoma phaeochromocytoma (bilateral) mucosal neuromas, GI symptoms, muscle hypotonia, chronic constipation due to hyperplasia of ______ _____ in intestinal wallMarfan-like signs:  connective tissue defects (abnormal fibrillin-1)f-1- ligand for TGFβ

Answer 23

1. 52. autonomic ganglia

Question 24

MEN IIbMost medullary thyroid carcinoma and phaeochromocytoma result from__ ____ only ~10% due to MEN mutation is in the ____gene – a proto-oncogene.gene product is a TK receptor; mutant is constitutively active without ligand.

Answer 24

1. new mutations2. Ret