Varying functions of cAMP

Question: Please clarify how an increase in cAMP on the one hand causes

  1. Bronchodilation and on the other hand increase in heart rate.

Answer:

As we know cAMP as a second messenger has several functions. It can activate different enzymes in different tissues, cause opening or closing of ion channels etc

Mechanism of Bronchodilation

1. Beta 2 agonists like Salbutamol stimulate Beta 2 receptors. This causes activation of the enzyme Adenyl cyclase (mediated by stimulating coupling protein Gs) and therefore increased conversion of ATP to cAMP (which is the major second messenger of Beta Receptor activation.
2. cAMP then produces relaxation of smooth muscle of the bronchi. This involves phosphorylation of myosin light chain kinase to an inactive form causing inhibition of contraction of smooth muscle. This prevents interaction between actin and myosin, resulting in vasodilation
3. This is the similar mechanism by which Beta 2 receptors mediate vasodilation in skeletal and coronary blood vessels

Mechanism of Increased Heart Rate
1. Beta 1 agonists like Dobutamine stimulate Beta 1 receptors. This causes activation of the enzyme Adenyl cyclase (mediated by stimulating coupling protein Gs) and therefore increased conversion of ATP to cAMP (which is the major second messenger of Beta Receptor activation.
2. cAMP then activates a Protein Kinase that causes opening of myocardial calcium channels, resulting in INCREASED calcium influx. This causes increased myocardial activity including increased interaction between actin and myosin resulting in increased heart rate and force of contraction

Thus this shows contrasting actions of cAMP where it is producing an inhibitory effect (bronchodilation) in one tissue and producing an excitatory effect (increased Heart Rate) in another tissue.

From

Nauman’s Textbook of Pharmacology

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