Pharmacology for Anaesthesia and Intensive Care

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Section IBasic principles

GTP^

ATP

NH 2

α

Adenylyl

cyclase

cAMP

COOH

γ

β

(c)

Figure 3.2.(Cont.)

lipid, phosphatidylinositol 4,5-bisphosphate (PIP 2 ), to form inositol triphosphate

(IP 3 )and diacylglycerol (DAG).

The two molecules formed have specific actions; IP 3 causes calcium release in

the endoplasmic reticulum, and DAG causes activation of protein kinase C, with a

variety of biochemical effects specific to the nature of the cell in question. Increased

calcium levels act as a trigger to many intracellular events, including enzyme action

and hyperpolarization. Again, the common messenger will cause specific effects

according to the nature of the receiving cellular subcomponent.

α 1 -Adrenoceptors, the muscarinic cholinergic types 1, 3 and 5 as well as

angiotensin II type 1 receptors exert their effects by activation of the Gq-proteins.

Membrane guanylyl cyclase.Some hormones such as atrial natriuretic peptide

mediate their actions via membrane-bound receptors with intrinsic guanylyl cyclase

activity. As a result cGMP levels increase and it acts as secondary messenger by

phosphorylation of intracellular enzymes.

Nitric oxide exerts its effects by increasing the levels of intracellular cGMP

by stimulating a cytosolic guanylyl cyclase rather than a membrane-bound

enzyme.

Membrane tyrosine kinase.Insulin and growth factor act through the tyrosine

kinase system, which is contained within the cell membrane, resulting in a wide

range of physiological effects. Insulin, epidermal growth factor and platelet-derived

growth factor all activate such tyrosine kinase-linked receptors.