Knowledge about the distribution and origins of peptide-containing nerves in the innervated and transplanted heart is lacking. Immunohistochemical and histochemical techniques were used to visualize human cardiac innervation before and after transplantation. In the recipient heart cardiac nerve fibers and fascicles displayed immunoreactivity for general neural (protein gene product 9.5 and synaptophysin) and Schwann cell markers (S-100). A major proportion of cardiac nerves displayed neuropeptide tyrosine and tyrosine hydroxylase immunofluorescence staining. Subpopulations of nerves contained somatostatin, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P- or neurokinin-like immunoreactivity, and acetylcholinesterase activity. Tissues from cardiac allografts (5 weeks to 63 months after transplantation) contained nerves and ganglion cells that were acetylcholinesterase positive and immunoreactive for the general neural markers. These nerves were less numerous than in recipient hearts and rarely displayed neuropeptide immunostaining. Atrial natriuretic peptide immunoreactivity was localized to myocardial cells in transplanted hearts as well as explanted recipient and postmortem hearts. While most human cardiac allografts remain functionally extrinsically denervated, they appear to contain viable intrinsic nerves, and myocardial cells retain the capacity to produce atrial natriuretic peptide.

Neuropeptide tyrosine (NPY) is the predominant peptide in the innervation of many human tissues and is considered to play a role in the regulation of blood flow, gastrointestinal secretion and motility, and renal function. Three NPY receptors have been identified (Y1, Y2, and Y3) and the cDNAs encoding the human Y1 and bovine Y3 receptors have recently been cloned. We have demonstrated the expression of the Yl receptor subtype in several fetal and adult human tissues, including the colon, kidney, adrenal gland, heart, and placenta. A single transcript was identified (%2.2 kb) and localized in tissue sections by in situ hybridization. In the colon the receptor is expressed in the mucosa and basal glands, as well as the myenteric and submucous plexuses. Y1 receptor mRNA was detected in renal collecting ducts, loop of Henle, and juxtaglomerular apparatus and in the syncytiotrophoblast layer of placental villi. Fetal aorta and adult intramyocardial, colonic, and renal blood vessels also exhibited receptor expression, localized to the intima as well as the media. The distribution of Yl receptor expression correlates with that of NPY-immunoreactive nerves and the apparent actions ofNPY in the intestine, kidney, and heart. Although the placenta is devoid of nerves, an NPY-like transcript was detected in the villous trophoblast layer. The results indicate a tissue-specific regulation of NPY Y1 receptor expression.Neuropeptide tyrosine (NPY) is an amidated 36-amino acid peptide found in both the central and peripheral nervous systems and is a member of a family of regulatory peptides which also includes peptide tyrosine tyrosine (PYY) (1). NPY is localized together with norepinephrine in sympathetic nerves and is widely distributed in the innervation of the human cardiovascular system, kidney, and gastrointestinal tract, as well as other organs (2, 3). In addition to its neural localization, NPY-like immunoreactivity has also been demonstrated in adrenal medullary cells (4) and the villous trophoblast layer in the placenta (5). PYY immunoreactivity exhibits a distinct distribution pattern and is localized to endocrine cells in the human colon (6). These peptides have both direct and indirect effects on blood flow, gastrointestinal secretion and motility (3), and renal function (7) (3,5,(9)(10)(11). Furthermore, the relevance of these studies to humans is uncertain due to species variation in both receptor distribution and peptide metabolism and the apparent difficulty in demonstrating specific NPY binding sites in human tissues (12). Following the recent cloning of human and bovine NPY receptor cDNA sequences (13,14), it is now possible to circumvent many of these problems by using specific molecular probes and in situ hybridization techniques to determine the localization of mRNA encoding NPY receptor subtypes. When expressed in vitro, the human receptor displays a rank order of agonist potency [NPY = PYY > [Leu31,Pro34]NPY >> NPY-(13-36)] characteristic of the Y1 receptor subtype (13). We have used radiolabeled...

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1 The localization and differential distribution of endothelin (ET) receptor subtypes (ETA and ETB) was investigated in sections of human placenta by use of quantitative in vitro autoradiography and receptor selective ligands.2 Specific, high density ['251]-ET-1 binding sites were localized to the decidua and foetal membranes as well as to arteries and veins in the chorionic plate and throughout the villous tree. Moderate to low density binding was found in the extravillous and villous trophoblast respectively. 6 ET may have a local autocrine or paracrine role in the placenta, acting via specific receptors to influence foetoplacental blood flow and other aspects of placental function.

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