Physiology and Pharmacology 10: (Challis) Adrenoceptors 2 Flashcards
Comment on the potency of Noradrenaline, Adrenaline and Isoprenaline on alpha and beta adrenoceptors - how was this discovered?
NA and A -> relatively similar moderate potency for both alpha and beta adrenoceptors
ISO -> low potency for alpha, very high potency for beta
Discovered with 2 biochemical assays (atrial contraction, vasoconstriction) -> very different responses in ISO potency for each response suggested 2 different mechanisms
Subtypes of adrenoceptor? What are they coupled to? Examples of function?
Alpha
a1a, a1b, a1d -> coupled positively to phospholipase C via Gq proteins
a2a, a2b, a2c -> coupled negatively to Adenyl cyclase via Gi proteins
- autoreceptors inhibit further release of noradrenaline via negative feedback
Beta
B1, B2, B3 -> coupled positively to adenyl cyclase via Gs proteins
- e.g. B1 in heart mediate positive inotropic+chronotropic effects,
- e.g. B2 in airways mediate bronchodilation, also vasodilation
Briefly describe GPCR mechanism of positive inotropy
Beta1adrenoceptors
-> Noradrenaline binds
- activates Gs protein + alpha subunit
- stimulates Adenyl Cyclase activity
- increases ATP to cAMP conversion
- cAMP activates PKA
- PKA phosphorylates + opens VOCC channels -> calcium influx
- increases contractility
What agonistic drugs might be used to act on the cardiovascular system, treating heart block, cardiac arrest etc.
B-adrenoceptor agonists e.g. adrenaline, isoprenaline
and/or B1-selective agonists e.g. dobutamine
What agonistic drugs might be used to act on the respiratory system, treating asthma etc.
Inhaled B2-selective agonists e.g. salbutamol, terbutaline resulting in bronchodilation
Examples of adrenoceptor antagonistic drugs?
Beta-blockers
e.g. propranolol, atenolol, used to treat cardiovascular disorders e.g. angina pectoris, hypertension
a1-adrenoceptor antagonists
e.g. prazosin, doxazosin
