Original paper discharge.13-15,19,20 Our findings about expres- sion of both KISS1 and KISS1R in type I cells, which represent the real chemoreceptive ele- ment of the carotid body, support a modulato- ry role of KISS1 on peripheral chemorecep- tion. Kisspeptins have been found to directly stimulate excitability of neurons, such as the granule cells of the dentate gyrus,21 and to modulate the release of other peptides, such as in hypophysis22 and islets of Langherans.23,24 Thus, also in the carotid body kisspeptins could act on excitability of type I cells and/or on their release of peptide neuro- modulators. Further functional studies will be necessary to clarify the effects of kisspeptins on chemosensory process in glomic cells. Kisspeptin receptor probably preferentially bind peptides locally released in the carotid body but circulating factors have also been reported to act on carotid body type I cells, and possible actions by blood-borne kisspeptins may not be excluded. The possible role of kisspeptins in the car- diovascular system has also recently been con- sidered. The carotid body is the structure in the body with the highest blood flow (about 1400 or 2000 mL/100 g/min in the cat, depend- ing on the technique for determination of tis- sue blood flow),25,26 and local changes in blood flow have been considered to be involved in carotid body chemoreceptor discharge.20,27,28 KISS1R and KISS1 have been found to be expressed in the endothelial cells of the aorta, coronary artery and umbilical vein and kisspeptins have been demonstrated to show potent vasoconstrictor action.10 In the present work anti-KISS1 and – KISS1R immunoreac- tions were also found in endothelial cells of some vessels, as a consequence a possible role of kisspeptins in the regulation of carotid body blood flow and, indirectly, in chemoreceptor discharge may be hypothesized. Kisspeptins could also show trophic actions on glomic cells. In the pre- and postnatal peri- ods the carotid body undergoes structural changes, mediated by trophic factors, includ- ing carotid body volume increase, proliferation of type I, type II, endothelial and Schwann cells lining peripheral nerve fibers and increased number of synapses between type I and II cells.15,29 Moreover, environmental stimuli (for instance, hypoxic, hyperoxic or inflammatory noxae) may also cause a series of morphologi- cal, cellular and biochemical changes.29-34 For instance, chronic hypoxia has been shown to increase O2 sensitivity in the carotid body through changes in molecular chemorecep- tors, ion channels and neurochemicals.35-37 The above changes are mediated by a wide series of trophic factors. It may also be hypothesized that kisspeptins released by type I cells may modulate the expression and effects of trophic factors in the carotid body. For instance, [page 80] [European Journal of Histochemistry 2011; 55:e14] kisspeptins have been found to increase BDNF expression in hippocampal slice cultures,38 and this growth factor has been identified in type I cells and nerve fibers of rat carotid body.15,39,40 In the literature, KISS1 and KISS1R have been found to be expressed in the dorsal root ganglia and to be upregulated after intraarticular injec- tion of the complete Freund’s adjuvant, suggest- ing possible involvement in chronic inflammato- ry pain.12 In the present work, expressions of both KISS1 and KISS1R were found in ganglion cells of the human and rat superior cervical gan- glia. Thus, it may be hypothesized a role of kisspeptins also in the modulation of the sympa- thetic function, probably mainly through autocrine or paracrine mechanisms. Figure 2. Anti-KISS1R immunohistochemistry in human (A,B,E,F) and rat (C,D,G,H) carotid bodies (A-D) and superior cervical ganglia (E-H), showing selective positivity of glomic type I cells and ganglionic cells, immunostaining being largely eliminated in neg- ative controls (B,D,F,H). Note also negativity of type II cells (asterisks) in the carotid body and of satellite cells in the superior cervical ganglia. Scale bars: A, D, 23.8 mm; B, C, E, F, 37.5 mm; G-H, 75 mm.