Membrane continued receptor sites

After initial experiments demonstrating that the antiserum was capable of completely inhibiting the binding of [ H]PbTx-3 to its receptor site in rat brain membranes (Figure 9), we began studies designed to evaluate potential of the antiserum for prophylaxis and treatment of brevetoxin intoxication (34). The tethered rat model was used, and surgical implantations were identical to those described above. Heart rate, core and peripheral body temperatures, lead VIO ECG, and arterial blood pressure were monitored continuously. Respiratory rate was recorded each 5 min for the first 3 hr, then each 15 min until 6 hr. 

Figure 6.3. Mechanism of action of heterotrimeric G-proteins. Upon receptor occupancy, the Ga-subunit binds GTP in exchange for GDP, and then moves in the membrane until it encounters its target enzyme, shown here as adenylate cyclase (alternatively, a phospholipase). The activated target enzyme then becomes functional. Inherent GTPase activity within the a-subunit then hydrolyses bound GTP to GDP, and the a-subunit dissociates from its target enzyme (which becomes inactive) and rebinds the / - and ysubunits. Upon continued receptor occupancy, further catalytic cycles of GTP exchange and target enzyme activation may occur. The scheme shown is for a stimulatory G-protein (Got,), but similar sequences of events occur with inhibitory G-proteins (Gcx,) except that the interaction of the a-subunit with adenylate cyclase will result in its inhibition. The sites of action of pertussis and cholera toxins are shown.

The bounding membrane of the neuron is typical of all cells. It is a continuous lipid bilayer sheet of thickness about 60-80 angstroms. Embedded in it, or passing through it, are numerous proteins and glycoproteins, many of which are found only in nerve cells. These have many functions. Some provide structural support to the membrane, but most form ion channels and receptor sites that are essential to nerve function. 

Once the neurotransmitter substance has interacted with the receptor sites on the postsynaptic membrane it must be deactivated so that it does not continuously excite or inhibit the membrane. There are at least three deactivation processes—mass transport away from the synaptic gap, reuptake, and enzymic degradation. 

A biological example of E° is the reduction of Fe(III) in the protein transferrin, which was introduced in Figure 7-4. This protein has two Fe(III)-binding sites, one in each half of the molecule designated C and N for the carboxyl and amino terminals of the peptide chain. Transferrin carries Fe(III) through the blood to cells that require iron. Membranes of these cells have a receptor that binds Fe(III)-transferrin and takes it into a compartment called an endosome into which H is pumped to lower the pH to —5.8. Iron is released from transferrin in the endosome and continues into the cell as Fe(II) attached to an intracellular metal-transport protein. The entire cycle of transferrin uptake, metal removal, and transferrin release back to the bloodstream takes 1-2 min. The time required for Fe(III) to dissociate from transferrin at pH 5.8 is —6 min, which is too long to account for release in the endosome. The reduction potential of Fe(IH)-transferrin at pH 5.8 is E° = —0.52 V, which is too low for physiologic reductants to reach. 

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