How can an increase in cAMP cause both an increase in contractility in the heart and

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tomhoney380
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^^
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macpatgh-Sheldon
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Can you complete your Q?
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tomhoney380
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(Original post by macpatgh-Sheldon)
Can you complete your Q?
Sorry!! Didn't realise I didn't finish it oh dear
So how can elevated cAMP cause both increased contractility in the heart and increased vasodilation due to msooth muscle relaxation?
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eeiiiiio
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Adrenaline activates cAMP through beta-adrenergic receptors in the heart muscle. cAMP is mediated by protein kinase A (PKA) which phosphorylates several proteins leading to influx of Ca2+ and increased muscle contraction.

Smooth muscle is different from heart muscle, using cAMP as an inhibitor of myosin light chain kinase (which is involved in muscle contraction). Increased levels of cAMP lead to increased inhibition - therefore relaxation.
There are other signalling molecules that cause vasodilation as well - such as cGMP and NO.
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macpatgh-Sheldon
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tomhoney380

Hi again,
The production of cyclic AMP catalysed by the enzyme adenyl cyclase is an important step in several biochemical actions that neurotransmitters and hormones use to effect their end-result.

First, ignoring this complex series of mechanisms with involvement of cAMP for a sec (sorry!), increase in contractility of the heart (mainly through a positive inotropic effect) is brought about by stimulation of beta-1 adrenoceptors [which also leads to a positive chronotropic effect resulting in relative tachycardia), and at the same time, one result of the stimulation of beta-2 adrenoceptors is to relax the smooth muscle of arterioles (mainly muscular arterioles). This in itself explains how an adrenoceptor agonist [most of which are non-selective for either beta-1 OR beta-2 receptors] can cause both an increase in myocardial contractility and peripheral vasodilatation. (Having said that, a catecholamine such as adrenaline [which is an agonist at both alpha- and beta-adrenoceptors] will lead predominantly to vasoconstriction through its alpha effect on vascular smooth muscle, which makes this muscle contract] [isoprenaline [isoproterenol in USA] is an almost purely beta agonist, so its effects would be v relevant to your Q].

Now the complex part:
- you might know that cAMP can be an intermediary in several processes in the nervous system. Firstly, cAMP has diverse functions including mediation of hormone action [the elucidation of the action of cAMP in bringing about the hyperglycaemic action of glucagon [via stimulation of glycogenolysis and inhibition of glycogenesis] is what led to Sutherland winning the Nobel prize ages ago], and activation of mast cell degranulation [which is the mechanism of immediate-type (Type I) hypesensitivity, the basis of allergic reactions].

cAMP exerts its effects via PKA (protein kinase A); the latter has four sub-units, two regulatory ones and two catalytic ones, and depending on which ones are activated, the result can be variable. Also, the actions of neurotransmitters in changing levels of cAMP pass through the stimulation of heterotrimeric G proteins, of which there is more than one e.g. alpha-s (subscript "s") stimulates adenylyl cyclase whereas alpha-i (subscript "i") inhibits adenylyl cyclase, with opposite effects, respectively, on levels of cAMP [oc this is a step before the production of cAMP so, strictly speaking, does not answer your Q).

Jpw1097

[are you able to add to/modify any of the above with your more recent training in molecular physiology?).

M.
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tomhoney380
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(Original post by macpatgh-Sheldon)
tomhoney380

Hi again,
The production of cyclic AMP catalysed by the enzyme adenyl cyclase is an important step in several biochemical actions that neurotransmitters and hormones use to effect their end-result.

First, ignoring this complex series of mechanisms with involvement of cAMP for a sec (sorry!), increase in contractility of the heart (mainly through a positive inotropic effect) is brought about by stimulation of beta-1 adrenoceptors [which also leads to a positive chronotropic effect resulting in relative tachycardia), and at the same time, one result of the stimulation of beta-2 adrenoceptors is to relax the smooth muscle of arterioles (mainly muscular arterioles). This in itself explains how an adrenoceptor agonist [most of which are non-selective for either beta-1 OR beta-2 receptors] can cause both an increase in myocardial contractility and peripheral vasodilatation. (Having said that, a catecholamine such as adrenaline [which is an agonist at both alpha- and beta-adrenoceptors] will lead predominantly to vasoconstriction through its alpha effect on vascular smooth muscle, which makes this muscle contract] [isoprenaline [isoproterenol in USA] is an almost purely beta agonist, so its effects would be v relevant to your Q].

Now the complex part:
- you might know that cAMP can be an intermediary in several processes in the nervous system. Firstly, cAMP has diverse functions including mediation of hormone action [the elucidation of the action of cAMP in bringing about the hyperglycaemic action of glucagon [via stimulation of glycogenolysis and inhibition of glycogenesis] is what led to Sutherland winning the Nobel prize ages ago], and activation of mast cell degranulation [which is the mechanism of immediate-type (Type I) hypesensitivity, the basis of allergic reactions].

cAMP exerts its effects via PKA (protein kinase A); the latter has four sub-units, two regulatory ones and two catalytic ones, and depending on which ones are activated, the result can be variable. Also, the actions of neurotransmitters in changing levels of cAMP pass through the stimulation of heterotrimeric G proteins, of which there is more than one e.g. alpha-s (subscript "s") stimulates adenylyl cyclase whereas alpha-i (subscript "i") inhibits adenylyl cyclase, with opposite effects, respectively, on levels of cAMP [oc this is a step before the production of cAMP so, strictly speaking, does not answer your Q).

Jpw1097

[are you able to add to/modify any of the above with your more recent training in molecular physiology?).

M.
Cheers man really appreciate it
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macpatgh-Sheldon
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No hassle Tom - btw, do you play hockey? There were 4 Toms in my hockey team at uni - looks like anyone with the name Tom has hockey in his blood, just like we Sikhs!!
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tomhoney380
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(Original post by macpatgh-Sheldon)
No hassle Tom - btw, do you play hockey? There were 4 Toms in my hockey team at uni - looks like anyone with the name Tom has hockey in his blood, just like we Sikhs!!
Yeah I played hockey for a bit for the medics team
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macpatgh-Sheldon
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Great stuff! Best fastest sport - and hockey is big in medicine, oc!
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