Nervous system
The NPY Y1R is widely distributed in the central nervous system. A study conducted on four normal human brains revealed that high levels of Y1R receptor mRNA were expressed in cortical areas and in the claustrum, while moderate levels were present in the nucleus accumbens, caudate nucleus, putamen, amygdaloid nuclei and arcuate and paraventricular nuclei of the hypothalamus. Moreover, a study conducted on prefrontal cortex of subjects affected by bipolar disorder, major depression, or schizophrenia revealed a progressive age-related decline in the expression of Y1R mRNA associated with a lack of coexpression with NPY neurons. Interestingly, there was no significant effect of suicide as a cause of death on Y1R mRNA expression levels. In fact, subjects with suicide as a cause of death tended to have higher Y1R mRNA expression levels, but these individuals were among the youngest ones (45 years old) in the population studied.

Periphery
Peripherally, Y1Rs are expressed mainly in arteries and veins, where they are associated with vasoconstriction and potentiation of other vasoconstrictors of neurogenic origin. Although limited, there is evidence of prejunctional Y1R inhibition of neurotransmitter release. Nonetheless, NPY Y1R is primarily located postjunctionally on vascular smooth muscle cells.
1) Colon
In vitro receptor autoradiography ([¹²⁵I]PYY) performed on normal human colonic tissue obtained from nine patients showed that Y1R is distributed only in vessels. No measurable levels of subtype Y1 was identified in smooth muscle, mucosa, muscularis mucosae, as well as in lymphoid follicles, myoenteric and submucosal plexus.
2) Heart
A study conducted on 20-week old fetal human hearts showed that Y1R is present on right ventricular endocardial endothelial cells. In particular, it is highly expressed at the level of the nucleus specifically at the perinucleoplasm and nuclear membrane levels, while lower levels were detected in the cytoplasm and the plasma membrane.
3) Dental pulp
NPY Y1R proteins were present in solubilized membrane preparations of both healthy and inflamed human gingival tissue by Western blotting. Major immunoreactive bands were detected at approximately 55 kDa due to a glycosylated form of the native receptor protein. By using the SwissProt glycosylation prediction packages NetNGlyc and NetOGly, authors confirmed that the human Y1R has potential N- and O-glycosylation sites. The expression of Y1R protein in both healthy and inflamed gingival tissue suggests that NPY could act via the Y1R to exert its tonic effects. Moreover, Y1R was expressed in human dental pulp with evidence of increased expression in carious compared with noncarious teeth. Y1R were localized to nerve fibres and inflammatory cells in the dental pulp of carious teeth.
4) Achilles tendons
Y1R is expressed in the tenocytes in the Achilles tendon. Specifically, Y1R is present within the smooth muscle of the blood vessel walls, but not in the endothelial layer of calcaneal tendons.
5) Skin
In human tissues, RT-PCR and immunocytochemistry studies suggested that Y1R is the primary receptor in human cutaneous circulation, supporting the findings that local non-noradrenergic mechanisms are entirely Y1R-based. Skin blood flow in humans is controlled through two branches of the sympathetic nervous system: a vasoconstrictor system and an active vasodilator system of uncertain neurotransmitter. In this context, NPY showed a vasoconstrictor effect in human subcutaneous arteries that had been dissected out of the abdominal regions from patients who underwent nonvascular disease surgeries (e.g., hernia). NPY decreased cutaneous blood flow via Y1R, with evidence for the additional involvement of postjunctional Y2R. This ability of NPY and Y1R to affect skin vascular conductance varies in accordance with relative innervations at specific sites.