Adenylate cyclase-cyclic adenosine monophosphate system

Glucagon appears to exert its effects on liver cells by a classic adenyl cyclase-cyclic adenosine monophosphate (cAMP) second messenger system (see Chapter 4).93 Glucagon binds to a specific receptor located on the hepatic cell membrane. This stimulates the activity of the adenyl cyclase enzyme that transforms adeno-... 

Abnormal G protein functioning dysregulates adenylate cyclase activity, phosphoinositide responses, sodiurrypotassiunVcalcium channel exchange, and activity of phospholipases. Abnormal cyclic adenosine monophosphate and phosphoinositide secondary messenger system activity. 

The measurement of TSH was originally based on bioassays such as the stimulation of colloid droplet formation in the guinea pig thyroid gland and the release of labeled thyroidal iodide into mouse blood. These early in vivo bioassays, however, were of limited sensitivity and precision and were not applicable to the measurement of TSH in unfractionated serum. Most TSH bioassays have involved the in vitro stimulation of thyroid cyclic adenosine monophosphate (cAMP) or adenylate cyclase activity. The rat FRTL-5 thyroid cell line is an example of a particularly convenient and precise assay system. Unfortunately, such methods require purification and concentration of TSH from serum before assay. Sensitive detection of TSH in unfractionated serum is possible using a cytochemical bioassay, but this procedure is technically difficult and time-consuming. At present, immunoassay is the procedure of choice for the measurement of serum TSH in the clinical laboratory. 

Biosynthesis of TRH occurs in a wide area of the hypothalamus and appears to be under the control of a nonribosomal (soluble) enzyme system, TRH synthetase (R5), which is activated by norepinephrine (G15). TRH is stored in the median eminence, from which is secreted into the hypophysial venous portal system to be transported to the anterior pituitary gland (R2). There it is specifically bound to membrane receptors (G13, W3) and activates adenyl cyclase, leading to increased production of cyclic adenosine monophosphate (K1). 

Fig. 24.3. Schematic representation of a 5 enkephalinergic nerve terminal. (1) Pro-opioid proteins (proenkephalin A) are synthesized in the cell nucleus. (2) Pro-opioid proteins undergo microtubular transport to the nerve terminal. (3) Active endogenous opioids (E) are cleaved from the pro-opioid proteins by the action of processing proteases. (4) The active peptides (E) are taken up and stored in presynaptic vesicles. (5) The peptides are released when the presynaptic neuron fires. (6) The endogenous opioid peptides bind to postsynaptic receptors and activate second messenger systems. (7) For all opioid receptors, the second messenger effect is primarily mediated by a G-inhibitory (Gj/o) protein complex, which promotes the inactivation of adenylate cyclase (AC), a decrease in intracellular cyclic-adenosine-3, 5 -monophosphate (cAMP),...

Recently, Szego and Davis (1967) provided evidence that an estrogen effect on the adenyl-cyclase system may be measured within 0.5 minute of systemic administration of the hormone. Uterine adenosine 3, 5 -monophosphate (cyclic AMP) was approximately doubled within... 

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