J

Tends to lower blood pressure

Increased water intake

Increased water intake

Blood pressure elevated

FIGURE 4-13 Scheme describing the regulation of body fluids. Abbreviations: NEP, norepinephrine; AVP-NP, Arg-VP-NP complex.

ligand binding shows that Tyr2 and Asn5 play critical roles in the interaction with receptor. Since Tyr2 is also involved in the interaction with NP, the hormone must be in the free form to interact with the receptor. Through this interaction, there is a stimulation of adenylate cyclase activity on the cytoplasmic side of the membrane. This process involves the transducing guanine nucleotide regulatory protein (Figure 4-16; see Chapter 1 for details of the activities of the G-protein subunits). ATP is converted to cyclic AMP on the cytoplasmic side of the cell membrane by the activated cyclase. Thyroid hormone may affect VP-sensitive adenylate cyclase. Thus, in hypothyroid rats, both the basal activity and the VP-stimulated activity of adenylate cyclase are decreased. Treatment with thyroxine restored the activity to normal levels. The elevated level of cyclic AMP, produced by VP, combines with the regulatory subunits (R) of inactive protein kinase (R2C2) to release the catalytically active subunit (C):

The detailed activation mechanism for PKA is presented in Chapter 1. The active protein kinase (PKa or C) appears to catalyze the phosphorylation of some specific protein possibly involved in the transport of aquaporins. These insert into the apical membrane to form channels for water uptake, which occurs by a process of free diffusion. Thus, the tight epithelial cell takes up little water in the unstimulated state and takes up a considerable amount of water in the VP-stimulated state due to a profusion of water channels created in the apical membrane. Presumably, water is transported across the cell and released at the basolat-eral side, involving water molecules transported by aquaporins (Figure 4-14).

Electron micrographs from toad bladder granular cell luminal membrane, untreated or treated with VP, show the aggregation of membrane particles after stimulation with VP. These observations suggest the possibility that water channels (AQP-CD) are being

FIGURE 4-14A Visualization of a water-transporting "aquaporin." These vesicles were detected by immunofluorescence in rat kidney cortex (A) and outer medulla (B) with a polyclonal antibody directed against a C-terminal peptide of aquaporin P3. This was detected at the basolateral membrane of collecting duct cells. Reproduced with permission from Ishibashi, K., Sasaki, S., Fushimi, K., Uchida, S., Kuwahara, M., Saito, H., Furukawa, T., Nakajing, K., Yama-guchi, Y„ Gojobori, T., and Marumo, F. (1994). Proc. Nat. Acad. Sci. USA 91, 6269-6273. B, Structure of aquaporins. Asterisk indicates the site of cysteine in aquaporin (AQP), AQP-CHIP and AQP-CD (collecting duct). AQP-CD is a VP-responsive aquaporin. The cysteine site is not present in MIWC or AQP3. Reproduced with permission from Knepper, M. A., (1994). Proc. Nat. Acad. Sci. USA 91, 6255-6258.

FIGURE 4-14A Visualization of a water-transporting "aquaporin." These vesicles were detected by immunofluorescence in rat kidney cortex (A) and outer medulla (B) with a polyclonal antibody directed against a C-terminal peptide of aquaporin P3. This was detected at the basolateral membrane of collecting duct cells. Reproduced with permission from Ishibashi, K., Sasaki, S., Fushimi, K., Uchida, S., Kuwahara, M., Saito, H., Furukawa, T., Nakajing, K., Yama-guchi, Y„ Gojobori, T., and Marumo, F. (1994). Proc. Nat. Acad. Sci. USA 91, 6269-6273. B, Structure of aquaporins. Asterisk indicates the site of cysteine in aquaporin (AQP), AQP-CHIP and AQP-CD (collecting duct). AQP-CD is a VP-responsive aquaporin. The cysteine site is not present in MIWC or AQP3. Reproduced with permission from Knepper, M. A., (1994). Proc. Nat. Acad. Sci. USA 91, 6255-6258.

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Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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