Biomedical subjects

S Sealfon

Publications and source records attributed to S Sealfon.

5 recordsLinked to original sources

PubMed2002

Lamprey GnRH-III acts on its putative receptor via nitric oxide to release follicle-stimulating hormone specifically.

Lamprey gonadotropin-releasing hormone-III (l-GnRH-III), the putative follicle-stimulating hormone (FSH)-releasing factor (FSHRF), exerts a preferential FSH-releasing activity in rats both in vitro and in vivo. To test the hypothesis that l-GnRH-III acts on its own receptors to stimulate gonadotropin release, the functional activity of this peptide at mammalian (m) leutinizing hormone (LH)RH receptors transfected to COS cells was tested. l-GnRH-III activated m-LHRH receptors only at a minimal effective concentration (MEC) of 10(-6) M, whereas m-LHRH was active at a MEC of 10(-9) M, at least 1,000 times less than that required for l-GnRH-III. In 4-day monolayer cultured cells, l-GnRH-III was similarly extremely weak in releasing either LH or FSH, and, in fact, it released LH at a lower concentration (10(-7) M) than that required for FSH release (10(-6) M). In this assay, m-LHRH released both FSH and LH significantly at the lowest concentration tested (10(-10) M). On the other hand, l-GnRH-III had a high potency to selectively release FSH and not LH from hemipituitaries of male rats. The results suggest that the cultured cells were devoid of FSHRF receptors, thereby resulting in a pattern of FSH and LH release caused by the LHRH receptor. On the other hand, the putative FSH-releasing factor receptor accounts for the selective FSH release by l-GnRH-III when tested on hemipituitaries. Removal of calcium from the medium plus the addition of EGTA, a calcium chelator, suppressed the release of gonadotropins induced by either l-GnRH-III or LHRH, indicating that calcium is required for the action of either peptide. Previous results showed that sodium nitroprusside, a releaser of nitric oxide (NO), causes the release of both FSH and LH from hemipituitaries incubated in vitro. In the present experiments, a competitive inhibitor of NO synthase, L-NG-monomethyl-L-arginine (300 micro M) blocked the action of l-GnRH-III or partially purified FSHRF. The results indicate that l-GnRH-III and FSHRF act on putative FSHRF receptors by a calcium-dependent NO pathway.

Animals↗

PubMed1998

Identification of three putative GnRH receptor subtypes in vertebrates.

The majority of vertebrates have two or three forms of gonadotropin-releasing hormone (GnRH), which appear to have arisen by successive gene duplication events. This suggests the possibility of concordant gene duplications of the GnRH receptor to produce two or more cognate receptors. Since the extracellular loop 3 (EC3) domain of mammalian GnRH receptors plays a role in distinguishing the different forms of GnRH, we have contemplated that the sequence of this domain will differ significantly in the putative cognate receptors. Degenerate oliognucleotides encoding the sequences of the transmembrane domains preceding and following EC3 were used for PCR amplification of genomic DNA from zebrafish (Brachydanio rerio), goldfish (Carassius auratus), African clawed frog (Xenopus laevis), chicken (Gallus domesticus), and lizard (Agama atra). Isolation and sequencing of specific clones revealed that they fell into three groups. Two of these were most similar to the mammalian pituitary GnRH receptor and were therefore designated Type IA and Type IB. The third form (designated Type II) was most different from the others and was identified in Xenopus, lizard, and human DNA. These findings support the concept of the existence of three distinct GnRH receptors, which have evolved in conjunction with three distinct GnRH ligand classes present in many vertebrates.

Amino Acid Sequence↗

PubMed1988

Functional expression of brain cholecystokinin and bombesin receptors in Xenopus oocytes.

Total RNA was extracted from 15-day-old whole rat brains. Microinjection of the RNA into Xenopus laevis oocytes induced electrophysiological responsiveness to cholecystokinin-8 (CCK) and bombesin (BBS) but not to corticotropin-releasing factor (CRF) or somatostatin. The responses to CCK and BBS were similar in shape, time course, and reversal potential to that induced by receptor mediated phospholipid breakdown and that which is induced by intracellular injection of IP3. These responses were not blocked by atropine or by mianserin, did not require extracellular Ca2+ and were completely suppressed by intracellular injection of EGTA.

Animals↗

PubMed1988

Activation of ionic currents in Xenopus oocytes by corticotropin-releasing peptides.

Oocytes of the African frog Xenopus laevis are shown by electrophysiological methods to possess receptors for corticotropin-releasing factor (CRF), arginine-vasopressin (AVP) and cholecystokinin (CCK). Oocytes surrounded by their follicular cell envelope responded to CRF or AVP with an outward hyperpolarizing current. This current was mediated by an increased conductance of K+ ions. Pretreatment with the adenylate cyclase activator forskolin or with the cAMP phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) potentiated the responses to these peptides indicating that the cAMP second messenger system may mediate the responses. Oocytes stripped of the follicular envelope, which cannot generate cAMP-dependent K+ currents, did not respond to either CRF or AVP. Oocytes exposed to CCK responded with an inward depolarizing current. This current was carried by an increased conductance to Cl-ions. Removal of the follicular cell layer did not affect the response to CCK. The shape, time course, and reversal potential of the Cl-current suggest that CCK acts through the phosphatidylinositol pathway.

Animals↗

PubMed1988

Reversible cerebral segmental vasoconstriction.

Vasoconstriction is not recognized as a cause of cerebrovascular disease except in the vasospasm seen following subarachnoid hemorrhage and possibly in migraine. However, we found four patients to have transient, fully reversible vasoconstriction and dilatation prominently involving arteries around the circle of Willis. All four patients were evaluated for severe headaches and fluctuating or recurring motor or sensory deficits. No cause for the clinical syndromes and angiographic abnormalities was found. Similar patients are reported in the literature under various nosologies. This newly recognized clinical-angiographic syndrome should be differentiated from other known causes of vessel constriction and dilatation; the precipitants of reversible vasoconstriction may then be better defined.

Adult↗