The prenatal diagnosis of spinal muscular atrophy

Trimethyltin (TMT) causes prominent neuronal damage and enhanced expression of neuropeptide Y in the hippocampus. We investigated expression of neuropeptide Y Y2 receptors after TMT intoxication. Markedly elevated (by 470%) concentrations of Y2 receptor mRNA were found in the suprapyramidal blade of the dentate granule cell layer after 5 days. Increases in the infrapyramidal blade were less prominent (by 198%). After 16 days, mRNA levels in both blades of the granule cell layer showed no significant difference from those in controls. Quantification of Y2 receptor-specific binding revealed no significant change at both 5 and 16 days after TMT intoxication. It is suggested, together with a previous report describing a similar increase of neuropeptide Y expression, that a transient expression of Y2 receptors in the dentate gyrus in the initial phase of TMT intoxication may be involved in mediating TMT-induced hippocampal damage.     

Marked decrease of neuropeptide Y Y2 receptor binding sites in the hippocampus in murine prion disease

Using autoradiographic binding methodology with monoiodinated peptide YY together with the agonists neuropeptide Y (NPY) and NPY (13-36), as well as in situ hybridization with oligonucleotide probes complementary to the NPY Y2 receptor (Y2-R) mRNA, we have studied whether or not intracerebral prion inoculation affects Y2-Rs in male CD-1 mice. Monoiodinated peptide YY binding, mainly representing Y2-Rs, was down-regulated by 85% in the CA1 strata oriens and radiatum and by 50-65% in the CA3 stratum oriens 110-140 days postinoculation. In the CA3 stratum radiatum, where the mossy fibers from the dentate granule cells project, there was a significant decrease in PYY binding at 110-120 days. Y2-R mRNA, moderately expressed both in the CA1 and CA3 pyramidal cell layers and the granule cell layer in the dentate gyrus, showed a slight, but not significant, decrease in CA3 neurons 130 days postinoculation. The results indicate that the accumulation of the scrapie prion protein in the CA1-3 region strongly inhibits NPY binding at the Y2-Rs, which, however, is only marginally due to reduced Y2-R mRNA expression. The loss of the ability of NPY to bind to inhibitory Y2-Rs may cause dysfunction of hippocampal circuits and may contribute to the clinical symptoms in mouse scrapie.     

Time-dependent changes in neurotrophic factor mRNA expression after kindling and long-term potentiation in rats

We compared the time-dependent changes in messenger ribonucleic acid (mRNA) levels for two neurotrophic factors after amygdala-kindled seizures and hippocampal long-term potentiation (LTP) in rats in vivo. The brain-derived neurotrophic factor (BDNF) mRNA levels in the bilateral granule cell layer of the dentate gyrus, increased significantly 1-4 h after stage 5 kindled seizures. Nerve growth factor (NGF) mRNA levels increased throughout the bilateral limbic regions more gradually than those of BDNF mRNA. The maximum levels in the dentate gyrus ipsilateral to stimulation (BDNF mRNA: 493%, NGF mRNA: 199% of control levels) occurred 2 h after seizures. As observed with kindling, BDNF and NGF mRNA expression increased in the dentate gyrus ipsilateral to stimulation also increased following LTP induced by the perforant path stimulation, with maximum levels occurring 2 h and 4 h, respectively, after stimulation, when they reached 284% and 189% of the control levels, respectively. These results suggest that BDNF and NGF are involved in enhancement of synaptic efficacy in the granule cells of the dentate gyrus in the hippocampus in kindling, not related to the neuronal excitability associated with seizure activity.     

Differential regulation by MK801 of immediate-early genes, brain-derived neurotrophic factor and trk receptor mRNA induced by a kindling after-discharge

Transient changes in immediate-early genes and neurotrophin expression produced by kindling stimulation may mediate secondary downstream events involved in kindling development. Recent experiments have demonstrated conclusively that both kindling progression and mossy fibre sprouting are significantly impaired by administration of the N-methyl-D-aspartate (NMDA) receptor antagonist MK801. To further examine the link between kindling, changes in gene expression and the NMDA receptor, we examined the effects of MK801 on neuronal induction of immediate-early genes, brain-derived neurotrophic factor (BDNF) and trk receptor mRNA expression produced by a single electrically induced hippocampal after-discharge in rats. The after-discharge produced a rapid (after 1 h) increase in Fos, Jun-B, c-Jun, Krox-24 mRNA and protein and Krox-20 protein in dentate granule neurons and a delayed, selective expression of Fos, Jun-D and Krox-24 in hilar interneurons. MK801 pretreatment produced a very strong inhibition of Fos, Jun-D and Krox-20 increases in dentate neurons but had a much smaller effect on Jun-B and c-Jun expression. MK801 did not inhibit Krox-24 expression in granule neurons or the delayed expression of Fos, Jun-D and Krox-24 in hilar interneurons. BDNF protein and trk B and trk C mRNA expression were also strongly induced in dentate granule cells 4 h following an after-discharge. MK801 abolished the increase in BDNF protein and trk B, but not trk C mRNA in granule cells at 4 h. These results demonstrate that MK801 differentially regulates the AD-increased expression of a group of genes previously identified as being likely candidates for an involvement in kindling. Because MK801 significantly retards the development of kindling and mossy fibre sprouting, it can be argued that those genes whose induction is not significantly attenuated by MK801 are unlikely to play an important role in the MK801-sensitive component of kindling and the changes in neural connectivity (mossy fibre sprouting) associated with kindling. Conversely, the role in kindling of those genes whose expression was significantly attenuated by MK801 (Fos, Jun-D, Krox-20, trkB and BDNF) requires further examination.     

Expression and regulation of the neuropeptide Y Y2 receptor in sensory and autonomic ganglia

The Y2 subtype of neuropeptide tyrosine (NPY) receptors (Y2R) and some neuropeptides have been studied with in situ hybridization in sensory and autonomic neurons of rat and monkey. Between 10% and 20% of the lumbar dorsal root ganglion (DRG) neuron profiles (NPs) contain Y2R mRNA in the rat and monkey. In rat DRGs Y2R mRNA is expressed in calcitonin gene-related peptide (CGRP)-positive, medium-sized, and large neurons, that is in a complementary fashion to the Y1R that is located in small CGRP neurons. In monkey DRGs Y2R mRNA is expressed mainly in small neurons. Peripheral axotomy up-regulates the Y2R in small and large DRG neurons in both species. Y2R and NPY mRNAs are colocalized in many large neurons in axotomized rat DRGs. Y2R mRNA is expressed in 50% of the NPs in the nodose ganglion with a modest increase after axotomy. Y2R mRNA is detected in a few NPs in normal rat superior cervical ganglia, with a marked increase after transection of the carotid nerves. No Y2R mRNA-positive, but many (approximately 30%) weakly Y1R mRNA-positive NPs were found in the sphenopalatine ganglion. Finally, Y2R mRNA levels increase in rat spinal motoneurons after axotomy. Thus, under normal circumstances NPY may act on Y1 and Y2Rs expressed, respectively, in small and large CGRP-positive DRG neurons in the rat. Y2R may be an important receptor in the viscero-sensory neurons. Y2Rs may be particularly important after axotomy serving as presynaptic and/or autoreceptors on rat DRG, superior cervical ganglion, and nodose ganglion neurons and as presynaptic receptors in monkey DRG neurons.     

Neuropeptide Y phase shifts the circadian clock in vitro via a Y2 receptor

The suprachiasmatic nuclei (SCN) contain a circadian clock whose activity can be recorded in vitro for several days. This clock can be reset by the application of neuropeptide Y. In this study, we focused on determination of the receptor responsible for neuropeptide Y phase shifts of the hamster circadian clock in vitro. Coronal hypothalamic slices containing the SCN were prepared from Syrian hamsters housed under a 14 h:10 h light:dark cycle. Tissue was bathed in artificial cerebrospinal fluid (ACSF), and the firing rates of individual cells were sampled throughout a 12 h period. Control slices received either no application or application of 200 nl ACSF to the SCN at zeitgeber time 6 (ZT6; ZT12 was defined as the time of lights off). Application of 200 ng/200 nl of neuropeptide Y at ZT6 resulted in a phase advance of 3.4 h. Application of the Y2 receptor agonist, neuropeptide Y (3-36), induced a similar phase advance in the rhythm, while the Y1 receptor agonist, [Leu31, Pro34]-neuropeptide Y had no effect. Pancreatic polypeptide (rat or avian) also had no measurable phase-shifting effect. Neuropeptide Y applied at ZT20 or 22 had no detectable phase-shifting effect. These results suggest that the phase-shifting effects of neuropeptide Y are mediated through a Y2 receptor, similar to results found in vivo.     

Status of somatostatin receptor messenger RNAs and binding sites in rat brain during kindling epileptogenesis

In situ hybridization histochemistry with somatostatin sst1-sst5 receptor messenger RNA-selective oligoprobes and quantitative receptor autoradiographic binding studies using [125I]Tyr3-octreotide, [Leu2,D-Trp22,125I-Tyr25]somatostatin-28 and [125I]CGP 23996 ([125I]c[Asn-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) were performed to determine the level of expression of somatostatin receptor messenger RNA and receptor binding sites in the hippocampal formation, limbic system and cerebral cortex of adult rats electrically kindled in the dorsal hippocampus. In control rats (implanted with electrodes but not electrically stimulated), the somatostatin-1 receptor-selective [125I]Tyr3-octreotide and the non-subtype-selective [Leu3,D-Trp22,125I-Tyr25]somatostatin-28 preferentially labelled the strata oriens and radiatum of the CA1 subfield of the hippocampus, the molecular layer of the dentate gyrus, the subiculum and presubiculum of the hippocampal formation, the inner layer of the frontal cortex, and the lateral and basolateral nuclei of the amygdala. The non-subtype-selective radioligand [125I]CGP 23996 (in 5 mM Mg2+ buffer) preferentially labelled the strata oriens and radiatum of the CA1 subfield of the hippocampus, the subiculum and the basolateral nucleus of the amygdala. Under conditions where primarily somatostatin-2 receptors were labelled, [125I]CGP 23996 (in 120 mM Na+ buffer) showed strong binding in the strata oriens and radiatum of the CA1 subfield of the hippocampus and the frontal cortex, whereas the dentate gyrus, subiculum and amygdala showed only weak signals. During and after kindling, no significant differences were observed between the ipsi- and contralateral sides of the hippocampus. A significant decrease (about 40%) of somatostatin receptor binding sites was observed in the molecular layer of the dentate gyrus with all radioligands (except [125I]CGP 23996 in Na+ buffer, which did not label this area) at stage 2 (pre-convulsive stage) and one week, but not one month, after stage 5 (generalized motor seizures). In contrast to somatostatin receptor binding, no alterations of the messenger RNA levels for sst1-sst5 receptors were found either at stage 2 or at stage 5. Similarly, no changes in receptor binding or messenger RNA levels were observed in the brain of rats which experienced a single afterdischarge. The present study shows a significant and selective decrease of somatostatin-1 receptor binding sites in the dentate gyrus of kindled rats. This is part of the plastic changes induced by kindling and may contribute to the increased sensitivity for the induction of generalized seizures during kindling.     

Expression cloning of a human brain neuropeptide Y Y2 receptor

The 36-amino acid peptide, neuropeptide Y (NPY), is a member of a peptide family that includes the endocrine peptides, peptide YY (PYY), and pancreatic polypeptide (PP). NPY receptors have been broadly subdivided into postsynaptic Y1 receptors and presynaptic Y2 receptors based on the preference of Pro34-substituted analogues for the Y1 receptors and carboxyl-terminal fragments for the Y2. A Y1 receptor has been cloned, and this receptor appears to mediate several effects of NPY, including vasoconstriction and anxiolysis in animal models. We report the cloning of a human brain Y2 receptor from a human brain library. Pools of clones were transiently expressed in COS-1 cells, and 125I-PYY binding pools were identified by autoradiography. After a single positive pool was detected in the original screening, a single clone was isolated by four rounds of sequential enrichment. The clone encoded a 381-amino acid protein of the heptahelix (seven TM) type. Amino acid identity of this receptor with the Y1 receptor was 31% overall with 40% identity in the TM regions. Comparison with the human PP1 receptor indicated 33% overall amino acid identity with 42% identity in the TM regions. Pharmacologically, the receptor exhibited high affinity for NPY, PYY, and carboxyl-terminal fragments of NPY and PYY. In addition, Pro34-substituted analogues had very low affinity. With the use of Northern blot analysis, high levels of Y2 mRNA were detected in a variety of brain regions with little expression in peripheral tissues. Thus, the receptor protein has the pharmacological properties and distribution of the human Y2 receptor.     

Altered neuropeptide Y Y1 responses in mesenteric arteries in rats with congestive heart failure

The aim of the present study was to elucidate if the potentiating effect of neuropeptide Y on various vasoactive agents in vitro is (1) altered in mesenteric arteries from rats with congestive heart failure and (2) mediated by the neuropeptide Y Y1 receptor. The direct vascular effects of neuropeptide Y and its modulating effects on the contractions induced by endothelin-1-, noradrenaline-, 5-hydroxytryptamine (5-HT)-, U46619-(9,11-dideoxy-11alpha, 9alpha-epoxymethano-prostaglandin F2alpha) and ATP, and acetylcholine-induced dilatations were studied in the presence and absence of the neuropeptide Y Y1 antagonist, BIBP3226 (BIBP3226?(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl ]-D-arginine-amide?). Neuropeptide Y, per se, had no vasoactive effect in the arteries. The potency of endothelin-1 was significantly decreased in congestive heart failure rats. Neuropeptide Y and neuropeptide Y-(13-36) potentiated the endothelin-1-induced contraction in congestive heart failure mesenteric arteries. In 20% of the congestive heart failure rats, sarafotoxin 6c induced a contraction of 31+/-4%. Neuropeptide Y also potentiated U46619- and noradrenaline-induced contractions but not 5-HT-induced contractions in congestive heart failure arteries. In sham-operated animals neuropeptide Y potentiated noradrenaline- and 5-HT-induced contractions. These potentiations were inhibited by BIBP3226. Acetylcholine induced an equipotent relaxation in both groups which was unaffected by neuropeptide Y. In conclusion, neuropeptide Y responses are altered in congestive heart failure rats. The potentiating effect differs between vasoactive substances. Neuropeptide Y Y1 and non-neuropeptide Y1 receptors are involved.     

Withdrawal of [corrected] estrogen increases hypothalamic neuropeptide Y (NPY) mRNA expression in ovariectomized obese rat

We determined the changes in neuropeptide Y (NPY) mRNA expression of the arcuate nucleus (ARC) in sham-operated (SHAM) and bilaterally ovariectomized (OVX) rats with estradiol (E2) supplement. Ovariectomy increases body weight gain for 3 weeks, accompanied by an increase of daily food intake. Ovariectomy significantly reduced serum corticosterone levels. E2 supplement reversed the effects of ovariectomy on body weight gain, food intake and serum corticosterone levels. Ovariectomy significantly increased NPY mRNA expression in the ARC. E2 supplement decreased NPY mRNA expression in the ARC of OVX rats. The present findings indicated that hypothalamic NPY mRNA expression, which involves the regulation of feeding behavior, are in parallel with circulating estrogen levels. Hypothalamic NPY mRNA expression may be important in the induction of hyperphagia after the withdrawal of estrogen by bilateral ovariectomy.     

Neuropeptide Y in human hand veins: pharmacologic characterization and interaction with cyclic guanosine monophosphate-dependent venodilators in vivo

The dorsal hand vein compliance technique was used to study direct vascular effects of human neuropeptide Y in vivo. Human neuropeptide Y is an endogenous vasoconstrictor peptide that is costored with norepinephrine in sympathetic nerve endings and coreleased with the catecholamine under various physiologic and pathologic conditions. Compared with the alpha 1-adrenergic agonist phenylephrine (geometric mean dose-rate that produces the half-maximal response [ED50]: 1.05 nmol/min; maximum venoconstriction [Emax] +/- SEM, expressed as a percentage of baseline compliance: 91% +/- 3%), human neuropeptide Y was nine times more potent (geometric mean ED50: 0.122 nmol/min; p < 0.001) but markedly less efficacious (Emax: 58% +/- 4%; n = 12; p < 0.001). Venoconstrictor effects of human neuropeptide Y lasted several hours and were unchanged by simultaneous administration of alpha-adrenergic antagonists but were readily reversed by nitroglycerin or bradykinin. The high responsiveness of subcutaneous veins to human neuropeptide Y indicates that human neuropeptide Y may regulate venous compliance and filling of the venous subcutaneous capacitance bed in vivo.     

A potent nonpeptide neuropeptide Y Y1 receptor antagonist, a benzodiazepine derivative

We describe here a nonpeptide neuropeptide Y Y1 receptor antagonist, 2,4-dioxo-1,5-bis(2-oxo-2-orthotolyl-ethyl)-3-[3-[3-([3-[3-(3-p iperidin-1-ylmethyl-phenoxy)-propylcarbamoyl]-propyl]-car bamoyloxymethyl)-phenyl]-ureido]-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diaz epine (Compound 1), which was previously synthesized as a linked type of dual cholecystokinin (CCK)-B and histamine H2 receptor antagonist. Compound 1 competitively inhibited [125I]peptide YY (PYY) binding to Y1 receptors in human neuroblastoma SK-N-MC cells with Ki of 6.4 +/- 1.0 nM, while it had no effect on [125I]PYY binding to Y2 or Y5 receptors even at 1 microM. Functionally, Compound 1 inhibited the Y1 receptor-mediated increase in cytosolic free Ca2+ concentration and Y1 receptor-mediated attenuation of cAMP accumulation in a dose-dependent manner with IC50 values of 95 +/- 5 and 320 +/- 10 nM in SK-N-MC cells, respectively. Neither its CCK-B receptor antagonistic moiety of Compound 1 (Compound 2) nor its histamine H2 receptor antagonistic moiety of Compound 1 (Compound 3) had any effect on [125I]PYY binding, suggesting that the entire structure of Compound 1 is essential for Y1 receptor blocking activity. It showed no significant activity (IC50 > 1 microM) in 30 receptor binding assays and 5 enzyme assays, with the exception of CCK-B and histamine H2 receptors. We conclude that Compound 1 is a useful molecule not only for studying the physiological role of neuropeptide Y but also for exploring more specific Y1 receptor antagonists.     

Elevated corticosterone is not required for the rapid induction of neuropeptide Y gene expression by an overnight fast

Fasting stimulates corticosterone (B) secretion and the expression and secretion of hypothalamic neuropeptide Y in rats. These studies tested the hypothesis that the rapid and marked fasting-induced increases in plasma B are responsible for stimulation of neuropeptide Y (NPY) gene expression. Plasma leptin and insulin were measured because they are also signals known to affect NPY messenger RNA (mRNA). Intact or adrenalectomized rats given a low fixed level of corticosterone (B replaced) were fasted for 48 h. NPY mRNA in the mediobasal hypothalamus, measured by nuclease protection assay, was elevated similarly above ad lib-fed controls in both intact and B replaced groups at 15 and 48 h after the onset of fasting. NPY immunoreactivity in the mediobasal hypothalamus increased between 3 and 48 h after onset of the fast in intact but not in B replaced groups. The fasting-induced decreases in leptin observed in intact rats at 48 h did not occur in B replaced rats. Fasting-induced decreases in insulin occurred in B replaced rats but not in intact rats. We conclude that: 1) elevated B is not required for fasting-induced increases in hypothalamic NPY gene expression; and 2) decreases in neither leptin nor insulin alone signal the changes that occur in NPY mRNA in fasted rats.     

Regulation of messenger ribonucleic acid for corticotropin releasing hormone receptor in the pituitary during stress

The mechanism regulating pituitary CRH receptors during stress was studied by analysis of the changes in CRH receptor messenger RNA (mRNA) and CRH binding after acute and repeated stress and CRH and vasopressin (VP) administration in intact and adrenalectomized rats. Acute stress caused time- and stress type-dependent changes in pituitary CRH receptor expression. In situ hybridization studies showed biphasic changes in CRH receptor mRNA after immobilization stress for 1 h and decreases by 2 h (P < 0.01). Increases (P < 0.01) were seen 4 and 8 h after the initiation of the stress, and a return to near basal levels by 12 and 18 h. A different pattern, with a decrease by 4 h (P < 0.01) and levels similar to controls after 12 and 18 h, was observed after a single ip injection of hypertonic saline (1.5 M NaCl). Binding autoradiography showed significant increases in pituitary CRH binding 4, 10, and 12 h after immobilization stress, but significant decreases 4, 12, and 18 h after ip hypertonic saline. In contrast, repeated immobilization or ip hypertonic saline for 8 or 14 days increased pituitary CRH receptor mRNA, and CRH binding was decreased. To determine the role of hypothalamic CRH and VP on these stress-induced changes, rats were injected for 14 days with CRH, VP, or their combination at doses mimicking stress levels in pituitary portal circulation (1 microgram/day sc). Repeated injection of CRH or VP increased CRH receptor mRNA and CRH binding (P < 0.05). CRH receptor mRNA levels further increased after combined administration of CRH and VP (P < 0.01), but CRH binding showed a tendency to decrease. The role of glucocorticoids on CRH receptor regulation was studied by analysis of the effects of stress on CRH receptor mRNA and CRH binding in adrenalectomized (ADX) rats with and without corticosterone replacement in the drinking water. Although in 6-day ADX rats pituitary CRH receptor mRNA levels were markedly reduced after acute immobilization, glucocorticoid replacement restored the stimulatory effect of stress to levels observed in intact rats. Similarly, a single sc injection of CRH (1 microgram) decreased CRH receptor mRNA in ADX rats but not in glucocorticoid-replaced ADX rats. CRH binding showed the expected decrease after ADX and was unchanged after stress or CRH injection. The increased pituitary CRH receptor mRNA after stress suggests that stress-induced CRH receptor down-regulation is due to increased receptor occupancy and internalization rather than to a decrease in receptor synthesis. The data suggest that increased hypothalamic secretion of CRH and VP mediates the delayed up-regulatory effect of stress on CRH receptor mRNA, and that resting levels of glucocorticoids are required for this effect. In addition, increased VP levels are permissive for the down-regulation of CRH binding induced by chronic pituitary exposure to stress levels of CRH.     

Metabotropic glutamate receptors mediate activation of NPY-Y2 receptor expression in the rat dentate gyrus

Neuropeptide Y-Y2 receptor mRNA and binding were investigated after local injection of excitatory amino acid receptor agonists into the rat hippocampus. The general metabotropic glutamate receptor (mGluR) agonist (1S,3R)ACPD (200 and 400 nmol) and the group I mGluR agonist DHPG (50 nmol) enhanced Y2 receptor mRNA levels in granule cells (by up to 470%) and [125I]PYY(3-36) binding in mossy fibers. The group I mGluR antagonist 4-CPG (200 nmol) inhibited the action of (1S,3R)ACPD. On the other hand, AMPA and NMDA enhanced Y2 receptor expression only at neurodegenerative doses (> 0.3 and 3 nmol, respectively). It is suggested that seizure-induced Y2 receptor expression in granule cells may be mediated by group I mGluRs.     

Long-term potentiation in vivo increases rat hippocampal tenascin-C expression

We investigated the expression of the extracellular matrix glycoprotein tenascin-C after induction of long-term potentiation (LTP) by high-frequency tetanization (HFT) in the rat dentate gyrus in vivo. Expression of tenascin-C was evaluated at the mRNA and protein levels by in situ hybridization and immunocytochemistry, respectively. Whereas no tenascin-C mRNA was detectable in control animals, an increase in tenascin-C mRNA levels was observed in the granule cell layer of the dentate gyrus 4 h after HFT. At 24 h after HFT, tenascin-C mRNA had returned to control levels. Expression of tenascin-C protein 4 h after HFT followed that of controls in that tenascin was detectable in the strata oriens and radiatum of CA1, in the molecular layer, and within a narrow area at the inner surface of the granule cell layer in the dentate gyrus. However, 24 h after HFT, additional patches of tenascin-C immunoreactivity were observed in the molecular layer of the dentate gyrus. No increase in tenascin mRNA or protein levels was detected in control animals that received no stimulation, low-frequency stimulation, or HFT in the presence of the N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid or the metabotropic glutamate receptor antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine. These observations implicate a role for tenascin-C in N-methyl-D-aspartate and metabotropic glutamate receptor-dependent changes accompanying induction and/or maintenance of LTP.     

Neuropeptide Y1 receptors in the rat genital tract

Using in situ hybridization and immunohistochemistry, the expression of type 1 neuropeptide Y (NPY) receptors (Y1-Rs) has been demonstrated in the rat genital tract. In the male Y1-R mRNA and Y1-R-like immunoreactivity (LI) were found in smooth muscles of predominantly arterioles and small arteries inside testis. Fibers showing NPY-LI could not be detected within testis but only in the tunica albuginea. These Y1-Rs are suggested to mediate vasoconstriction, possibly activated by NPY released from nerves in the tunica albuginea. In the female rat Y1-R mRNA, but not Y1-R-LI was found in vascular smooth muscles of arteries in the ovary and oviduct. In the oviduct Y1-R mRNA was also detected in the non-vascular smooth muscle layer. Fibers showing NPY-LI were found around blood vessels both in the ovary and oviduct. In the female genital tract also Y1-Rs may thus be involved in regulatory mechanisms mediating, for example, vasoconstriction.