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Biomedical subjects

P Hedlund

Publications and source records attributed to P Hedlund.

At least 37 records · Page 2Linked to original sources
PubMed1995

Receptor-receptor interactions and their relevance for receptor diversity. Focus on neuropeptide/dopamine interactions.

Receptor diversity in combination with receptor-receptor subtype specific interactions, which can be antagonistic or synergistic in character, markedly increase plasticity in WT and VT in the nervous system. In this way switching among transmission lines for the various DA receptor subtypes becomes possible. Some of these aspects are supported by our work on selective modulation of D2 receptors by CCK and NT. Selective regulation of D2 receptors via CCK-8 receptor subtypes and NT receptors may underlie CCK/DA interactions and NT/DA interactions in the basal ganglia. These studies underline the importance of receptor-receptor interactions exerted at the membrane level between neuropeptide receptors and D2 receptors, which are determined at least in part by the ongoing activity at D1 receptors. In the case of both CCK/D2 and NT/D2 receptor interactions, it has been possible, by means of intrastriatal and intraaccumbens microdialysis, to obtain a functional correlate to the receptor interactions found in the membrane preparations from the striatum. Schizophrenia may be in part related to reduced release of CCK and/or NT peptides or to alterations in their receptor interactions with the D2 receptor. This view may lead to new therapeutic approaches.

Animals↗
PubMed1995

Pituitary adenylate cyclase-activating polypeptide, helospectin, and vasoactive intestinal polypeptide in human corpus cavernosum.

1. The distribution and effects of pituitary adenylate cyclase-activating polypeptide (PACAP-27 and -38), helospectin (Hel-1 and Hel-2), and vasoactive intestinal polypeptide (VIP), were investigated in isolated preparations of human corpus cavernosum (CC). 2. Immunohistochemistry revealed coinciding profiles of nerve structures that showed immunoreactivities for VIP and PACAP, and VIP and Hel. Confocal microscopy showed the co-existence of VIP- and PACAP-immunoreactivities, and VIP- and Hel-immunoreactivities in most (90%) varicose nerve structures. 3. As determined by radioimmunoassay, the amounts of VIP, PACAP-27, and PACAP-38 in the preparations were 61.7 +/- 11.6, 0.1 +/- 0.05, and 3.7 +/- 0.5 pmol g-1 wet weight of tissue (pmol g-1 wet wt.), respectively. In tissue from patients with diabetes, the content of VIP was lower (13.7 +/- 0.5 pmol g-1 wet wt.), whereas that of PACAP (-27 and -38) was unchanged. 4. Cyclic nucleotide levels were determined in preparations exposed to PACAP-27, PACAP-38, Hel-1, Hel-2, and VIP. All the peptides, but Hel-2, significantly increased the concentrations of cyclic AMP, whereas the levels of cyclic GMP were unchanged. 5. The peptides concentration-dependently relaxed noradrenaline-contracted preparations. The order of potency was VIP > PACAP 27 > Hel-1 > Hel-2 > PACAP-38. 6. Hel-1, VIP and PACAP-27 effectively counteracted electrically induced contractions. At 10(-6) M, the highest peptide concentration used, the inhibitory effects obtained reached 96 +/- 3%, 87 +/- 6%, and 80 +/- 3%, respectively. 7. The results suggest that PACAP and Hel-1 are co-localized with VIP in nerve structures within the human cavernous tissue, and that the peptides are effective relaxants of CC preparations in vitro. The role of the investigated peptides for penile erection remains to be established.

Adult↗
PubMed1995

Distribution and function of nitric oxide-containing nerves in canine corpus cavernosum and spongiosum.

Specimens of penile erectile tissue from the corpus cavernosum (CC) and corpus spongiosum (CS) of beagle dogs were investigated with reference to morphological and functional aspects of the nitric oxide (NO) system. Using immunohistochemistry, the smooth muscle bundles of the CC were found to contain a rich innervation, as seen by the pan-neuronal marker, protein gene product 9.5. A large number of nerves also stained positively for acetylcholine esterase. There was a moderate to rich supply of nerves containing NO synthase, which was frequently co-localized with vasoactive intestinal polypeptide. CS preparations from the proximal penis (the spongious bulb) had an innervation similar to that of the CC. However, CS preparations from the distal penis had a distinctly lower density of nerves than the proximal part, and spongious tissue from the glans penis was practically devoid of nerves. In isolated preparations of proximal and distal CC and CS, contracted by noradrenaline, electrical field stimulation (EFS) produced frequency-dependent relaxations. The responses were less pronounced in preparations from the distal penis, particularly in the CS. Pre-treatment with the NO-synthesis inhibitor NG-nitro-L-arginine abolished all relaxations. Carbachol effectively relaxed noradrenaline-contracted strips. The responses were similar in proximal preparations from the CC and CS, and significantly less pronounced in strips from the distal penis. NG-nitro-L-arginine significantly reduced the relaxant effect of carbachol. Preparations of spongious tissue from the glans penis did not react to high potassium solution, addition of noradrenaline, or EFS. The results demonstrate regional differences within the CS, both in innervation and functional responses.

Acetylcholinesterase↗
PubMed1995

Estrogen receptors in the human male bladder, prostatic urethra, and prostate. An immunohistochemical and biochemical study.

The distribution and quantity of estrogen receptors (ERs) in the human male bladder, prostatic urethra and the prostate were studied in eight males with recurrent papillomas of the bladder or monosymptomatic hematuria (median age 61 years), 14 men undergoing transurethral resection due to benign prostatic hyperplasia (median age 70 years), and nine men undergoing cystectomy due to malignant tumour of the bladder (median age 70 years). In the first group of patients, biopsies for immunohistochemical examination were obtained from the bladder vault, bottom, both side-walls, the trigone area, and the mid-portion of the prostatic urethra, and in the second group from three locations of the prostatic urethra (bladder neck, mid-portion and veramontanum). In the third group, tissue specimens were taken from the vault of the bladder, prostatic urethra, and the prostate, for immunohistochemical as well as biochemical analysis. In the first group, ERs were found in three out of eight specimens of the prostatic urethra, and in one of these, ERs were confined to periurethral glands. ERs could not be demonstrated in any of the bladder-biopsies. In the second group, ERs were not found in the bladder neck, but were seen in four preparations from the veramontanum and in two from the midportion of the urethra. ERs were located in the urothelium and periurethral glands. In the third group, ERs were seen immunohistochemically in the prostatic urethra (two cases) and the prostatic stromal tissue (two cases). ERs could be demonstrated in the bladder neither by immunohistochemistry nor biochemically.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Effects of nicorandil on human isolated corpus cavernosum and cavernous artery.

Nitric oxide (NO) released from nonadrenergic-noncholinergic (NANC) nerves seems to be a principal mediator of the relaxation of penile erectile tissue necessary for erection, and drugs acting by release of NO have been shown to produce erection when injected intracorporeally into impotent patients. By producing hyperpolarization, K+ channel openers are effective in relaxing isolated penile erectile tissue from rabbit and man, and can produce tumescence and erection when injected intracorporeally into animals. Nicorandil is classified as a K+ channel opener, but it also acts as a donor of NO. In the present study, the effects of nicorandil on isolated preparations from human corpus cavernosum (CC) and deep cavernous artery (Acc) were compared with those of cromakalim (K+ channel opener) and SIN-1 (NO donor). Nicorandil produced a concentration-dependent relaxation of CC and Acc preparations. The relaxations obtained at the highest nicorandil concentration used (10(-4) M.) were 75 +/- 3% and 66 +/- 4% in CC preparations contracted by noradrenaline and endothelin-1, respectively. The corresponding effects in Acc preparations were 70 +/- 14% and 73 +/- 5%. Glibenclamide (blocking ATP-dependent K+ channels) significantly reduced the nicorandil-induced relaxation in CC, but not in Acc. Methylene blue (believed to block soluble guanylate cyclase) reduced nicorandil's relaxant effect in CC, although statistical significance was not obtained. NG-nitro-L-arginine 10(-4) M. (NO synthase inhibitor) did not significantly influence the effect of nicorandil on precontracted preparations in either tissue. In CC preparations contracted by electrical field stimulation, nicorandil and cromakalim concentration dependently inhibited the responses. This effect was significantly counteracted by glibenclamide. It is concluded that nicorandil is effective in relaxing human CC chiefly by its K+ channel opening action, and to some extent by its ability to release NO. For nicorandil's relaxing effect on Acc, ATP dependent K+ channels seem to be of limited importance. If effective in impotent patients, the drug may represent a new, interesting approach to the treatment of erectile dysfunction.

Adult↗
PubMed1991

Neuropeptide Y/angiotensin II interactions in central cardiovascular regulation of the rat.

Neuropeptide Y (NPY)/angiotensin II (ANG II) interactions have been studied in the central nervous system of the rat in view of their co-distribution and their opposing role in central cardiovascular control using quantitative receptor autoradiography and measurements of mean arterial blood pressure (MAP), heart rate and respiratory rate. The receptor autoradiographical experiments show that incubation with ANG II (10 nM) produces an increase in porcine (p) iodinated NPY-(1-36) [125I]pNPY-(1-36) binding within the dorsal strip (ds) of the nucleus tractus solitarius (nTS). Immunocytochemical analysis of intracisternally injected ANG II indicated that it could reach this area, in addition to the periventricular gray of the medulla oblongata, the pons and the periventricular part of the dorsal thalamus and dentate gyrus. Furthermore, a threshold dose of ANG II given intracisternally (3 nmol/rat) together with a dose (75 pmol/rat) of pNPY-(1-36) close to its ED50 value for reducing MAP, not only counteracts the vasodepressor action of pNPY-(1-36) but also leads to a marked increase of MAP. Also the bradycardic and bradypneic actions of pNPY-(1-36) are counteracted by this dose of ANG II. In contrast, a threshold dose of pNPY-(1-36) does not counteract the pressor action of an ED50 dose of ANG II (10 nmol/rat) but even enhances the peak pressor action of ANG II. These results may be explained on the basis that central ANG II receptor activation leads to an uncoupling of the NPY Y1 receptor, which mediate the vasodepressor action of pNPY-(1-36) and which is preferentially labeled by [125I]pNPY-(1-36).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1991

Activation of 5-hydroxytryptamine1A receptors increases the affinity of galanin receptors in di- and telencephalic areas of the rat.

Since galanin in vitro selectively increases the KD value of 5-HT1A receptors without altering the binding of 5-HT1B or 5-HT2 receptors, we have studied whether 5-HT1A receptor activation in turn may affect galanin binding in the ventral di- and telencephalon and the substantia nigra of the rat. As analyzed by autoradiography, the binding of 125I-galanin was increased by about 55% in the presence of 3-30 nM of 8-OH-2-(di-n-propylamino)-tetralin (DPAT) in the paraventricular thalamic nucleus, the nucleus reuniens and rhomboideus, the zona incerta, the medial and the lateral hypothalamus, and the medial and the lateral amygdaloid area, but not in the pars compacta of the substantia nigra, which lacks 5-HT1A binding sites. DPAT (10 nM) reduced the IC50 values of galanin at 125I-galanin binding sites by approximately 55% within all the analyzed di- and telencephalic regions. The overall increase in BO values was 50 +/- 11%. Using the filter wipe technique in cryostat sections at Bregma -2.8 mm covering all the brain regions at this level, DPAT (10 nM) decreased the IC50 values of galanin from 21.6 +/- 1.1 nM (control) to 15.5 +/- 0.9 nM, and increased the BO values by 19.4 +/- 4.1%. In membrane preparations from the ventral di- and telencephalon, DPAT decreased the IC50 values of galanin binding sites by 20 +/- 3% at 100 nM of DPAT. This effect could be completely blocked by the specific 5-HT1A receptor antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗