Page 291 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

!
Enzyme-Linked Cell Surface Receptors For hormones in that they induce a specific cell re-
Messenger Substances sponse with the difference being that they acti-
These (G protein-independent) receptors, to- vate a different type of signaling cascade in the
gether with their cytosolic domains, act as cell. They are lipid-soluble substances that
enzymes that are activated when a messenger freely penetrate the cell membrane.
binds to the receptor’s extracellular domain. Steroid hormones bind to their respective
There are five classes of these receptors: cytoplasmic receptor protein in the target cell
1. Receptor guanylyl cyclases convert GTP (! D). This binding leads to the dissociation of
into the second messenger cGMP, which acti- inhibitory proteins (e.g., heat shock protein,
vates protein kinase G (PKG; see below). The HSP) from the receptors. The hormone–recep-
Hormones and Reproduction factors (GF) such as e.g., E[epidermal]GF, PDGF, where it activates (induces) or inhibits the
atriopeptin receptor belongs to this class.
tor protein complex (H–R complex) then mi-
(! C),
tyrosine
kinases
grates to the cell nucleus (translocation),
Receptor
2.
phosphorylate proteins (of same or different
type) at the OH group of their tyrosyl residues.
transcription of certain genes. The resulting in-
The receptors for insulin and various growth
crease or decrease in synthesis of the respec-
tive protein (e.g., AIPs; ! p. 182) is responsible
N[nerve]GF, F[fibroblast]GF, H[hepatocyte]GF,
for the actual cell response (! D).
and I[insulin-like]GF-1 belong to this class of
Triiodothyronine (T 3; ! p. 286ff.) and cal-
receptors.
citriol (! p. 292) bind to their respective re-
ceptors). These receptors are hormone-acti-
and PDGF) are often transferred inside the cell via
vated transcription factors. Those of calcitriol
binding of two receptors (dimerization; C1a ! C1b)
11 Signals regarding first messenger binding (e.g., EGF ceptor proteins in the cell nucleus (nuclear re-
can induce the transcription of calcium-bind-
and subsequent mutual phosphorylation of their cy-
tosolic domain (autophosphorylation, ! C1b). The ing protein, which plays an important role in
receptor for certain hormones, like insulin and IGF-1, interstitial Ca 2+ absorption (! p. 262).
is from the beginning a heterotetramer (α 2" 2) that
undergoes autophosphorylation before phosphory- Recent research indicates that steroid hormones and
lating another protein (insulin receptor substrate-1, calcitriol also regulate cell function by non-genomic
IRS-1) that in turn activates intracellular target pro- control mechanisms.
teins containing SH2 domains (! C2).
Nitric Oxide as a Transmitter Substance
3. Receptor serine/threonine kinases, which In nitrogenergic neurons and endothelial tis-
like the TGF-! receptor, function similar to ki- sues, nitric (mon)oxide (NO) is released by
nases in Group 2, the only difference being that Ca /calmodulin-mediated activation of neu-
2+
they phosphorylate serine or threonine resi- ronal or endothelial nitric oxide synthase
dues of the target protein instead of tyrosine (NOS) (! E). Although NO has a half-life of only
residues (as with PKC; see above). a few seconds, it diffuses into neighboring cells
4. Tyrosine kinase-associated receptors are (e.g., from endothelium to vascular myocytes)
those where the receptor works in combina- so quickly that it activates cytoplasmic guany-
tion with non-receptor tyrosine kinases lyl cyclase, which converts GTP into cGMP
(chiefly proteins of the Src family) that (! E). Acting as a second messenger, cGMP ac-
phosphorylate the target protein. The recep- tivates protein kinase G (PKG), which in turn
tors for STH, prolactin, erythropoietin and decreases the cytosolic Ca 2+ concentration
numerous cytokines belong to this group. [Ca ]i by still unexplained mechanisms. This
2+
5. Receptor tyrosine phosphatases remove
phosphate groups from tyrosine residues. The ultimately leads to vasodilatation (e.g., in coro-
nary arteries).
CD45 receptor involved in T cell activation
belongs to this group. Penile erections are produced by cGMP-mediated
vasodilatation of the deep arteries of the penis
Hormones with Intracellular Receptors (! p. 308). The erection can be prolonged by drugs
Steroid hormones (! p. 270ff., yellow areas), that inhibit cGMP-specific phosphodiesterase type 5,
thereby delaying the degradation of cGMP (e.g., sil-
278 calcitriol and thyroid hormones are like other
denafil citrate = Viagra!).
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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