catecholamiens Flashcards
cortex develops from _____;invades retroperitoneal mesenchyme about week 5medulla derived from ___ ____;about week 7 of development
- mesothelium2. neural crest
PNMT is activated by_____ and ____
sympathetic nerves and glucocorticoids
cholinergic innervation from the ___nerve stimulates exocytosis from chromaffin granules–> release catecholamines
- splanchnic
?% adrenaline?% noradrenalineany one cell secretes either adrenaline OR noradrenaline
- 20In most cells, granules contain PNMT and noradrenaline is methylated to adrenaline
β -adrenoceptor activates ___–>____ cAMPα1-adrenoceptor activates ____–> ↑ ____ and ____α2-adrenoceptor activates ____ –> ____ in ____
- Gαs , increase2. Gαq –> IP3 and DAG3. Gαi. decrease in cAMP
Binding to β2 adrenoceptorsAdrenaline is bound to amino acid sidechains in helices ___, ___ and __Conformational change in thereceptor when adrenaline binds
3, 5 and 7
What receptors are involved in ↑ :…. glycogenolysis lipolysis gluconeogenesis secretion of insulin and glucagon heart rate
- β22. β33. α14.β25.β1
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
- β1 2. α13. α14. α1
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
- β2 2. β13. β24. α1
Continuous exposure to adrenaline ________multiple GPCRs___phosphorylates several serine and threonine residues in the cytosolic domain of ALL GPCRs,
- 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
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
- third2. β-arrestin,β-Arrestin binds clathrin (and other proteins), –> endocytosis and internalisation of the receptor
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
- adrenocortical (steroid)
PhaeochromocytomaImmediate management:α antagonist (e.g. )β antagonist (e.g. )Scan using radioactive compound (MIBG), taken up by catecholamine-producing tissues
- phenoxybenzamine2. propranolol
Catecholamines are rapidly clearedand catabolised by: methylation: ________ oxidation: ____ and _______ _______
- COMT2. MAO and aldehyde dehydrogenase
β adrenoceptor has a very ___ extracellular N-terminus, inadequate to be a LBD.Instead, 7 membrane helices from ____binding pocket
- short2. hydrophilic
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 ___)
- Noradrenaline2. Adrenaline3. Adrenaline 4. Noradrenaline5.adrenaline6. noradrenaline Both can dilate the pupil (if applied at high concentrations) and induce piloerection.
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
- hypercalcaemia2. gastrinoma
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 ?
- thymus, lung or stomach2. flushing, diarrhoea, palpitations, hypotension, right-sided heart disease3. family history and tumoursin 2 of: parathyroid, pancreatic islets, anterior pituitary
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
- meninMenin also interacts with TGF-β signalling at the level of SMAD
How can a loss of function mutation have autosomal dominant inheritance?
a) a somatic mutation occurs in the normal allele, –>2 defective allelesb) inactivation of the normal allele
Multiple Endocrine Neoplasia – MEN type IIMEN IIa (~__% of MEN II) medullary thyroid carcinoma very aggressive; early ____required phaeochromocytoma (bilateral) parathyroid hyperplasia
- 95 2. thyroidectomy
MEN IIb (~___% of MEN II) medullary thyroid carcinoma phaeochromocytoma (bilateral) mucosal neuromas, GI symptoms, muscle hypotonia, chronic constipation due to hyperplasia of ______ _____ in intestinal wallMarfan-like signs: connective tissue defects (abnormal fibrillin-1)f-1- ligand for TGFβ
- autonomic ganglia
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.
- new mutations2. Ret
